Disease Information
General Information of the Disease (ID: DIS00020)
| Name |
Staphylococcus meningitis
|
|---|---|
| ICD |
ICD-11: 1B54
|
| Resistance Map |
Type(s) of Resistant Mechanism of This Disease
ADTT: Aberration of the Drug's Therapeutic Target
DISM: Drug Inactivation by Structure Modification
EADR: Epigenetic Alteration of DNA, RNA or Protein
IDUE: Irregularity in Drug Uptake and Drug Efflux
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
23 drug(s) in total
Chloramphenicol
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Drug Inactivation by Structure Modification (DISM)
|
||||
| Key Molecule: Chloramphenicol acetyltransferase gene (CATS) | [4] | |||
| Resistant Disease | Streptococci infection [ICD-11: 1B54.2] | |||
| Resistant Drug | Chloramphenicol | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Enterococcus faecalis strain JH2-2 | 1320322 | ||
| Enterococcus faecalis strain pIP1326g | 1351 | |||
| Enterococcus faecalis strain pIP655 | 1351 | |||
| Enterococcus faecalis strain pIP683 | 1351 | |||
| Enterococcus faecalis strain pIP687 | 1351 | |||
| Enterococcus faecium strain pIP1182 | 1352 | |||
| Enterococcus faecium strain pIP1535 | 1352 | |||
| Enterococcus faecium strain pIP1538 | 1352 | |||
| Enterococcus faecium strain pIP1539 | 1352 | |||
| Enterococcus faecium strain pIP1687 | 1352 | |||
| Enterococcus faecium strain pIP713 | 1352 | |||
| Streptococci strain A451 | 36470 | |||
| Streptococci strain A453 | 36470 | |||
| Streptococci strain A456 | 36470 | |||
| Streptococci strain B109 | 1319 | |||
| Streptococci strain B117 | 1319 | |||
| Streptococci strain B118 | 1319 | |||
| Streptococci strain B120 | 1319 | |||
| Streptococci strain B126 | 1319 | |||
| Streptococci strain B127 | 1319 | |||
| Streptococci strain BM132 | 1319 | |||
| Streptococci strain BM137 | 36470 | |||
| Streptococci strain BM140 | 1319 | |||
| Streptococci strain G44 | 1320 | |||
| Streptococci strain G52 | 1320 | |||
| Streptococci strain G54 | 1320 | |||
| Experiment for Molecule Alteration |
Southern blotting assay | |||
| Mechanism Description | An assay based on the utilization of degenerate primers that enable enzymatic amplification of an internal fragment of cat genes known to be present in gram-positive cocci was developed to identify the genes encoding chloramphenicol resistance in streptococci and enterococci. The functionality of this system was illustrated by the detection of cat genes belonging to four different hydridization classes represented by the staphylococcal genes catpC221, catpC194, catpSCS7, and the clostridial gene catP, and by the characterization of a new streptococcal cat gene designated catS. | |||
| Key Molecule: Chloramphenicol acetyltransferase (CAT) | [5] | |||
| Resistant Disease | Staphylococcus intermedius infection [ICD-11: 1B54.3] | |||
| Resistant Drug | Chloramphenicol | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli strain XL-1 Blue | 562 | ||
| A Staphylococcus intermedius strain isolated from a purulent skin infection of a dog | 1285 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | However, little is known about CmR in staphylococcal species pathogenic to animals. Recently, CmR plasmids have been isolated from 'equine's. sciuri, 'canine' S. epidermidis, 'porcine' S. hyicus and 'canine' S. intermedius strains. All staphy- lococcal CmR plasmids encode a common resistance mechanism, namely an inducible Cm acetyltransferase (CAT). | |||
Ciprofloxacin XR
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ciprofloxacin XR | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ciprofloxacin XR | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ciprofloxacin XR | |||
| Molecule Alteration | Expression | Acquired |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. S. aureus SA113 (pTUS20) harboring a plasmid carrying the staphylococcal norA gene was 16 to 64 times more resistant to relatively hydrophilic quinolones. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ciprofloxacin XR | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Daptomycin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: Cardiolipin synthase 2 (CLS2) | [8] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Daptomycin | |||
| Molecule Alteration | Missense mutation | p.A23V+p.T33N+p.L52F+p.F60S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus isolates | 1280 | ||
| Staphylococcus aureus MRSA32 [A5948] | 553567 | |||
| Staphylococcus aureus RN6607 [A8115] | 553573 | |||
| Staphylococcus aureus RN9120 [A8117] | 553574 | |||
| Experiment for Molecule Alteration |
Whole genome sequence assay; Allelic frequency measurement assay | |||
| Experiment for Drug Resistance |
Broth microdilution method assay | |||
| Mechanism Description | Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2. | |||
| Key Molecule: Phosphatidylglycerophosphate synthase (PGSA) | [8] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Daptomycin | |||
| Molecule Alteration | Missense mutation | p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus isolates | 1280 | ||
| Staphylococcus aureus MRSA32 [A5948] | 553567 | |||
| Staphylococcus aureus RN6607 [A8115] | 553573 | |||
| Staphylococcus aureus RN9120 [A8117] | 553574 | |||
| Experiment for Molecule Alteration |
Whole genome sequence assay; Allelic frequency measurement assay | |||
| Experiment for Drug Resistance |
Broth microdilution method assay | |||
| Mechanism Description | Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2. | |||
| Key Molecule: Phosphatidylglycerol lysyltransferase (MPREF) | [9] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Daptomycin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli BL21(DE3) | 469008 | ||
| Experiment for Molecule Alteration |
TLC and Western blot analysis | |||
| Experiment for Drug Resistance |
Epsilometer test (E test) assay | |||
| Mechanism Description | MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane. | |||
Diclofenac
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Drug Inactivation by Structure Modification (DISM)
|
||||
| Key Molecule: Beta-lactam-inducible penicillin-binding protein (MECA) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: Autolysins enzymes (ALTE) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: Beta-lactamase (BLAC) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: Aminoacyltransferase FemA (FEMA) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: Aminoacyltransferase FemB (FEMB) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: Formin binding protein 1 (FNBP1) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: Mitochondrial trans-2-enoyl-CoA reductase (MECR) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1 (MURA1) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
| Key Molecule: UDP-N-acetylmuramate-L-alanine ligase (MURC) | [10] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Diclofenac | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| Cell Pathway Regulation | mecA/blaZ pathway | Activation | hsa01501 | |
| In Vivo Model | Murine skin and soft tissue infection model | Mus musculus | ||
| Experiment for Molecule Alteration |
Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay | |||
| Experiment for Drug Resistance |
CCK-8 assay | |||
| Mechanism Description | High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants. | |||
Doxorubicin
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Transmembrane protein 94 (TMEM94) | [1] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Doxorubicin | |||
| Molecule Alteration | Methylation | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | S. aureus isolates | 41687 | ||
| Experiment for Molecule Alteration |
PCR; Docking assay | |||
| Experiment for Drug Resistance |
Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay | |||
| Mechanism Description | This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance. | |||
Enoxacin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Enoxacin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Enoxacin | |||
| Molecule Alteration | Expression | Acquired |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. S. aureus SA113 (pTUS20) harboring a plasmid carrying the staphylococcal norA gene was 16 to 64 times more resistant to relatively hydrophilic quinolones. | |||
Fosfomycin
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Transmembrane protein 94 (TMEM94) | [1] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Fosfomycin | |||
| Molecule Alteration | Methylation | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | S. aureus isolates | 41687 | ||
| Experiment for Molecule Alteration |
PCR; Docking assay | |||
| Experiment for Drug Resistance |
Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay | |||
| Mechanism Description | This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance. | |||
Framycetin
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Transmembrane protein 94 (TMEM94) | [1] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Framycetin | |||
| Molecule Alteration | Methylation | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | S. aureus isolates | 41687 | ||
| Experiment for Molecule Alteration |
PCR; Docking assay | |||
| Experiment for Drug Resistance |
Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay | |||
| Mechanism Description | This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance. | |||
Gentamicin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: Phosphatidylglycerol lysyltransferase (MPREF) | [9] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Gentamicin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli BL21(DE3) | 469008 | ||
| Experiment for Molecule Alteration |
TLC and Western blot analysis | |||
| Experiment for Drug Resistance |
Epsilometer test (E test) assay | |||
| Mechanism Description | MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane. | |||
Ketoprofen
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Transmembrane protein 94 (TMEM94) | [1] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Ketoprofen | |||
| Molecule Alteration | Methylation | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | S. aureus isolates | 41687 | ||
| Experiment for Molecule Alteration |
PCR; Docking assay | |||
| Experiment for Drug Resistance |
Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay | |||
| Mechanism Description | This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance. | |||
Macrolides
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Erythromycin resistance protein (ERM33) | [11] | |||
| Resistant Disease | Staphylococcus sciuri infection [ICD-11: 1B54.1] | |||
| Resistant Drug | Macrolides | |||
| Molecule Alteration | Expression | Gene recombination |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus sciuri plasmid pSCFS1 | 1296 | ||
| Experiment for Molecule Alteration |
Sequence analysis | |||
| Experiment for Drug Resistance |
MIC assay | |||
| Mechanism Description | Staphylococcus sciuri Gene erm(33), Encoding Inducible Resistance to Macrolides, Lincosamides, and Streptogramin B Antibiotics, Is a Product of Recombination between erm(C) and erm(A). | |||
Moxifloxacin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Moxifloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Moxifloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Norfloxacin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Norfloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Norfloxacin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Norfloxacin | |||
| Molecule Alteration | Expression | Acquired |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. S. aureus SA113 (pTUS20) harboring a plasmid carrying the staphylococcal norA gene was 16 to 64 times more resistant to relatively hydrophilic quinolones. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Norfloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Novobiocin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: DNA topoisomerase 4 subunit B (PARE) | [12] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Novobiocin | |||
| Molecule Alteration | Missense mutation | p.G78S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus RN4220 | 1280 | ||
| Experiment for Molecule Alteration |
PCR amplification and DNA sequence assay | |||
| Experiment for Drug Resistance |
Twofold agar dilution method assay | |||
| Mechanism Description | At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin. | |||
| Key Molecule: DNA topoisomerase 4 subunit B (PARE) | [12] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Novobiocin | |||
| Molecule Alteration | Missense mutation | p.R136G |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus RN4220 | 1280 | ||
| Experiment for Molecule Alteration |
PCR amplification and DNA sequence assay | |||
| Experiment for Drug Resistance |
Twofold agar dilution method assay | |||
| Mechanism Description | At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin. | |||
| Key Molecule: DNA topoisomerase 4 subunit B (PARE) | [12] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Novobiocin | |||
| Molecule Alteration | Missense mutation | p.A89G |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus RN4220 | 1280 | ||
| Experiment for Molecule Alteration |
PCR amplification and DNA sequence assay | |||
| Experiment for Drug Resistance |
Twofold agar dilution method assay | |||
| Mechanism Description | At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin. | |||
| Key Molecule: DNA topoisomerase 4 subunit B (PARE) | [12] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Novobiocin | |||
| Molecule Alteration | Missense mutation | p.S128L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus RN4220 | 1280 | ||
| Experiment for Molecule Alteration |
PCR amplification and DNA sequence assay | |||
| Experiment for Drug Resistance |
Twofold agar dilution method assay | |||
| Mechanism Description | At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin. | |||
Ofloxacin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ofloxacin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. | |||
| Key Molecule: Quinolone resistance protein NorA (NORA) | [7] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Ofloxacin | |||
| Molecule Alteration | Expression | Acquired |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli HB101 | 634468 | ||
| Staphylococcus aureus strain SA113 | 1280 | |||
| Experiment for Molecule Alteration |
Dideoxy chain-termination method assay | |||
| Mechanism Description | The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. S. aureus SA113 (pTUS20) harboring a plasmid carrying the staphylococcal norA gene was 16 to 64 times more resistant to relatively hydrophilic quinolones. | |||
Oxacillin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Epigenetic Alteration of DNA, RNA or Protein (EADR)
|
||||
| Key Molecule: Membrane-associated protein TcaA (tcaA) | [2] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Oxacillin | |||
| Molecule Alteration | Expression | . |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Experiment for Molecule Alteration |
qPCR | |||
| Experiment for Drug Resistance |
E-test assay | |||
| Mechanism Description | The MIC of penicillin plus clavulanate decreased from 3 mg/L to 0.064 mg/L and that of oxacillin decreased from 16 to 0.5 mg/L when?tcaA?was knocked out in the LAC strain. Compared with wild-type MRSA isolates, when?tcaA?was deleted, all selected strains were more susceptible to beta-lactams. Susceptibility to ceftobiprole was restored in the ceftobiprole-resistant strain when?tcaA?was deleted.?tcaA?knockout caused "log-like" abnormal division of MRSA, and?tcaA?deficiency mediated low expression of?mecA, ponA, and?murA2. tcaA is a potential resistance breaker target for beta-lactams, including ceftobiprole, in MRSA. | |||
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Epigenetic Alteration of DNA, RNA or Protein (EADR)
|
||||
| Key Molecule: Membrane-associated protein TcaA (tcaA) | [2] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Oxacillin | |||
| Molecule Alteration | Expression | . |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Experiment for Molecule Alteration |
qPCR | |||
| Experiment for Drug Resistance |
E-test assay | |||
| Mechanism Description | The MIC of penicillin plus clavulanate decreased from 3 mg/L to 0.064 mg/L and that of oxacillin decreased from 16 to 0.5 mg/L when?tcaA?was knocked out in the LAC strain. Compared with wild-type MRSA isolates, when?tcaA?was deleted, all selected strains were more susceptible to beta-lactams. Susceptibility to ceftobiprole was restored in the ceftobiprole-resistant strain when?tcaA?was deleted.?tcaA?knockout caused "log-like" abnormal division of MRSA, and?tcaA?deficiency mediated low expression of?mecA, ponA, and?murA2. tcaA is a potential resistance breaker target for beta-lactams, including ceftobiprole, in MRSA. | |||
Quinine
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Transmembrane protein 94 (TMEM94) | [1] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Quinine | |||
| Molecule Alteration | Methylation | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | S. aureus isolates | 41687 | ||
| Experiment for Molecule Alteration |
PCR; Docking assay | |||
| Experiment for Drug Resistance |
Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay | |||
| Mechanism Description | This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance. | |||
Rifabutin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.A473T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.Q468K |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.D471Y |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L+p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.A473T+p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifabutin | |||
| Molecule Alteration | Missense mutation | p.D471Y+p.S486L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
Rifampin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Epigenetic Alteration of DNA, RNA or Protein (EADR)
|
||||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.A473T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.Q468K |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.D471Y |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L+p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.H481N+p.A473T+p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifampin | |||
| Molecule Alteration | Missense mutation | p.D471Y+p.S486L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
Rifapentine
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.A473T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.Q468K |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.D471Y |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.H481N+p.L466S |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.H481N+p.I527M |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.H481N+p.S529L+p.Q465R |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.H481N+p.A473T+p.A477T |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
| Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) | [13] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Rifapentine | |||
| Molecule Alteration | Missense mutation | p.D471Y+p.S486L |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus aureus strain T109 | 1280 | ||
| Staphylococcus aureus strain T112 | 1280 | |||
| Staphylococcus aureus strain T113 | 1280 | |||
| Staphylococcus aureus strain T115 | 1280 | |||
| Staphylococcus aureus strain T118 | 1280 | |||
| Staphylococcus aureus strain T124 | 1280 | |||
| Staphylococcus aureus strain T161 | 1280 | |||
| Staphylococcus aureus strain T166 | 1280 | |||
| Staphylococcus aureus strain T20 | 1280 | |||
| Staphylococcus aureus strain T211 | 1280 | |||
| Staphylococcus aureus strain T212 | 1280 | |||
| Staphylococcus aureus strain T23 | 1280 | |||
| Staphylococcus aureus strain T236 | 1280 | |||
| Staphylococcus aureus strain T23aa | 1280 | |||
| Staphylococcus aureus strain T23aac | 1280 | |||
| Staphylococcus aureus strain T23bb | 1280 | |||
| Staphylococcus aureus strain T248 | 1280 | |||
| Staphylococcus aureus strain T249 | 1280 | |||
| Staphylococcus aureus strain T25 | 1280 | |||
| Staphylococcus aureus strain T250 | 1280 | |||
| Staphylococcus aureus strain T262 | 1280 | |||
| Staphylococcus aureus strain T264 | 1280 | |||
| Staphylococcus aureus strain T295 | 1280 | |||
| Staphylococcus aureus strain T296 | 1280 | |||
| Staphylococcus aureus strain T297 | 1280 | |||
| Staphylococcus aureus strain T36 | 1280 | |||
| Staphylococcus aureus strain T38 | 1280 | |||
| Staphylococcus aureus strain T382 | 1280 | |||
| Staphylococcus aureus strain T38aa | 1280 | |||
| Staphylococcus aureus strain T38bb | 1280 | |||
| Staphylococcus aureus strain T397 | 1280 | |||
| Staphylococcus aureus strain T398 | 1280 | |||
| Staphylococcus aureus strain T399 | 1280 | |||
| Staphylococcus aureus strain T4 | 1280 | |||
| Staphylococcus aureus strain T400 | 1280 | |||
| Staphylococcus aureus strain T401 | 1280 | |||
| Staphylococcus aureus strain T402 | 1280 | |||
| Staphylococcus aureus strain T403 | 1280 | |||
| Staphylococcus aureus strain T404 | 1280 | |||
| Staphylococcus aureus strain T46 | 1280 | |||
| Staphylococcus aureus strain T59 | 1280 | |||
| Staphylococcus aureus strain T66 | 1280 | |||
| Experiment for Molecule Alteration |
DNA sequencing assay | |||
| Experiment for Drug Resistance |
Agar dilution method assay | |||
| Mechanism Description | Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance. | |||
Sparfloxacin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Sparfloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Sparfloxacin | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Tetracycline
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Tetracycline efflux MFS transporter Tet(38) (TET38) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Tetracycline | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of tet38 expression. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Tetracycline | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of tet38 expression. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain. | |||
Vancomycin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: Phosphatidylglycerol lysyltransferase (MPREF) | [9] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Vancomycin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli BL21(DE3) | 469008 | ||
| Experiment for Molecule Alteration |
TLC and Western blot analysis | |||
| Experiment for Drug Resistance |
Epsilometer test (E test) assay | |||
| Mechanism Description | MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane. | |||
Clinical Trial Drug(s)
2 drug(s) in total
Pristinamycin IA
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Erythromycin resistance protein (ERM33) | [11] | |||
| Resistant Disease | Staphylococcus sciuri infection [ICD-11: 1B54.1] | |||
| Resistant Drug | Pristinamycin IA | |||
| Molecule Alteration | Expression | Gene recombination |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus sciuri plasmid pSCFS1 | 1296 | ||
| Experiment for Molecule Alteration |
Sequence analysis | |||
| Experiment for Drug Resistance |
MIC assay | |||
| Mechanism Description | Staphylococcus sciuri Gene erm(33), Encoding Inducible Resistance to Macrolides, Lincosamides, and Streptogramin B Antibiotics, Is a Product of Recombination between erm(C) and erm(A). | |||
Cetrimide
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Cetrimide | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Cetrimide | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Investigative Drug(s)
8 drug(s) in total
Alpha-Mangostin-4
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Multiple efflux pumps MepA and NorA | [14] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | Alpha-Mangostin-4 | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | Efflux pumps of MRSA2 signaling pathway | Regulation | N.A. | |
| In Vitro Model | Male SPF-grade ICR mice | 5833 | ||
| Methicillin-resistant Staphylococcus aureus | 5833 | |||
| Experiment for Molecule Alteration |
SEM assay; TEM assay; EtBr accumulation assay; qRT-PCR; Western blot assay; Bocillin FL PBP binding assay; beta-Lactamase activity assay | |||
| Experiment for Drug Resistance |
MIC assay; Time-Kill assay; Hemolytic activity assay; Cytotoxicity assay | |||
| Mechanism Description | In this study, potential agents to combat MRSA resistance were explored, with the antibacterial activity of synthesized alpha-mangostin (alpha-MG) derivatives being evaluated alongside investigations into their cellular mechanisms against MRSA2. alpha-MG-4, featuring an allyl group at C3 of the lead compound alpha-MG, restored the sensitivity of MRSA2 to penicillin, enrofloxacin, and gentamicin, while also demonstrating improved safety profiles. Although alpha-MG-4 alone was ineffective against MRSA2, it exhibited an optimal synergistic ratio in vitro when combined with these antibiotics. This significant synergistic antibacterial effect was further confirmed in vivo using a mouse skin abscess model. Additionally, the synergistic mechanisms revealed that alpha-MG-4 was associated with changes in membrane permeability and inhibition of the MepA and NorA genes, which encode the efflux pumps of MRSA2. alpha-MG-4 also inhibited PBP2a expression, potentially by occupying a crucial binding site in a dose-dependent manner.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA)'s resistance to multiple antibiotics poses significant health and safety concerns. A novel alpha-mangostin (alpha-MG) derivative, alpha-MG-4, was first identified as a xanthone-based PBP2a inhibitor that reverses MRSA2 resistance to penicillin. The synergistic antibacterial effects of alpha-MG-4 were linked to increased cell membrane permeability and the inhibition of genes involved in efflux pump function. | |||
Homidium bromide
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Homidium bromide | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Homidium bromide | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Lincosamides
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Erythromycin resistance protein (ERM33) | [11] | |||
| Resistant Disease | Staphylococcus sciuri infection [ICD-11: 1B54.1] | |||
| Resistant Drug | Lincosamides | |||
| Molecule Alteration | Expression | Gene recombination |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Staphylococcus sciuri plasmid pSCFS1 | 1296 | ||
| Experiment for Molecule Alteration |
Sequence analysis | |||
| Experiment for Drug Resistance |
MIC assay | |||
| Mechanism Description | Staphylococcus sciuri Gene erm(33), Encoding Inducible Resistance to Macrolides, Lincosamides, and Streptogramin B Antibiotics, Is a Product of Recombination between erm(C) and erm(A). | |||
MA-D1
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
|
Aberration of the Drug's Therapeutic Target (ADTT)
|
||||
| Key Molecule: Glucosamine-fructose-6-phosphate aminotransferase (GlmS) | [15] | |||
| Sensitive Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Sensitive Drug | MA-D1 | |||
| Molecule Alteration | Expression | Down-regulation |
||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | Methicillin-resistant Staphylococcus aureus | 5833 | ||
| BABL/C female mice | 5833 | |||
| Experiment for Molecule Alteration |
Gel-based protein profiling assay; MS analysis; Enzymatic activity assay; Thermal shift assay; SPR assay; RNA isolation assay; RT-PCR | |||
| Experiment for Drug Resistance |
Resistance development assay; Hemolysis assay; Cytotoxicity assay | |||
| Mechanism Description | Marinopyrrole A derivative MA-D1 shows anti-MRSA activity by targeting GlmS to inhibit cell wall biosynthesis. This discovery provides a novel target and a lead for developing new antibiotics. | |||
Midecamycin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Drug Inactivation by Structure Modification (DISM)
|
||||
| Key Molecule: Oleandomycin glycosyltransferase oleD (OLED) | [16] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Midecamycin | |||
| Molecule Alteration | Expression | Acquired |
||
| Experimental Note | Discovered Using In-vivo Testing Model | |||
| In Vitro Model | Pseudomonas aeruginosa strain B-2099/18 | 287 | ||
| Experiment for Molecule Alteration |
SDS-PAGE analysis | |||
| Experiment for Drug Resistance |
Broth microdilution antifungal susceptibility test assay | |||
Moenomycin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: Phosphatidylglycerol lysyltransferase (MPREF) | [9] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Moenomycin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli BL21(DE3) | 469008 | ||
| Experiment for Molecule Alteration |
TLC and Western blot analysis | |||
| Experiment for Drug Resistance |
Epsilometer test (E test) assay | |||
| Mechanism Description | MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane. | |||
Quinolones
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Irregularity in Drug Uptake and Drug Efflux (IDUE)
|
||||
| Key Molecule: Quinolone resistance protein NorB (NORB) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Quinolones | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
|
Unusual Activation of Pro-survival Pathway (UAPP)
|
||||
| Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) | [6] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Quinolones | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli | 668369 | ||
| Experiment for Molecule Alteration |
DNA microarray hybridization assay | |||
| Experiment for Drug Resistance |
Serial twofold agar dilutions assay | |||
| Mechanism Description | MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. | |||
Quinupristin/Dalfopristin
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Drug Inactivation by Structure Modification (DISM)
|
||||
| Key Molecule: Virginiamycin B lyase (VGBB) | [17] | |||
| Resistant Disease | Staphylococcus aureus infection [ICD-11: 1B54.0] | |||
| Resistant Drug | Quinupristin/Dalfopristin | |||
| Molecule Alteration | Expression | Inherence |
||
| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | Escherichia coli BL21(DE3) | 469008 | ||
| Experiment for Molecule Alteration |
PCR amplification and sequence alignments assay | |||
| Experiment for Drug Resistance |
Spectrophotometric and fluorometric assay | |||
| Mechanism Description | Virginiamycin B lyase (Vgb) inactivates the quinupristin component of Synercid by lactone ring opening and the enzyme promotes this reaction by intramolecular Beta-elimination without the involvement of a water molecule. Replacement of the conserved active site residues His228, Glu268, or His270 with alanine reduces or abolishes S. cohnii Vgb activity. Residue Lys285 in S. cohnii Vgb is spatially equivalent to the S. aureus Vgb active site residue Glu284. | |||
References
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