Drug (ID: DG00186) and It's Reported Resistant Information
Name
Rifampin
Synonyms
Abrifam; Archidyn; Arficin; Arzide; Benemicin; Benemycin; Dipicin; Doloresum; Eremfat; Famcin; Fenampicin; RFP; RMP; Ramp; Rifa; Rifadin; Rifadine; Rifagen; Rifaldazin; Rifaldazine; Rifaldin; Rifam; Rifamor; Rifampicin; Rifampicina; Rifampicine; Rifampicinum; Rifamsolin; Rifaprodin; Rifcin; Rifinah; Rifobac; Rifoldin; Rifoldine; Riforal; Rimactan; Rimactane; Rimactazid; Rimactizid; Rimazid; Rimycin; Sinerdol; Tubocin; Rifamicin AMP; Rifampicin SV; Rifampicine [French]; Rifampin [USAN]; Rifamycin AMP; Ba 41166; AZT + Rifampin; BA-41166E; Ba 41166/E; DRG-0109; Dione 21-acetate; L-5103; L-5103 Lepetit; Piperine & Rifampicin; R-Cin; R/AMP; Reserpine & Rifampicin; Rifadin (TN); Rifadin I.V; Rifampicin & EEP; Rifampicin & Propolis; Rifampicina [INN-Spanish]; Rifampicinum [INN-Latin]; Rifampin (USP); Rimactan (TN); Rimactane (TN); Rimycin (TN); Sinerdol (TN); Tubocin (TN); Rifadin I.V.; Rifampicin (JP15/INN); Rifampicin[INN:BAN:JAN]; Rifadin, Rimactane, Rifampicin, Rifampin; 1-b]furan-21-yl acetate; 3-(((4-Methyl-1-piperazinyl)imino)-methyl)rifamycin; 3-(((4-Methyl-1-piperazinyl)imino)methyl)rifamycin SV; 3-(4-Methylpiperazinyliminomethyl)-rifamycin SV; 3-(4-Methylpiperazinyliminomethyl)rifamycin SV; 3-([(4-Methyl-1-piperazinyl)imino]methyl)rifamycin SV; 3-[(4-Methyl-1-piperazinyl)iminomethyl]rifamycin SV; 3-[[(4-Methyl-1-piperazinyl)imino]-methyl]rifamycin; 8-(((4-Methyl-1-piperazinyl)imino)methyl)rifamycin SV; 8-(4-Methylpiperazinyliminomethyl) rifamycin SV; 8-[[(4-Methyl-1-piperazinyl)imino[methyl]rifamycin; 8-[[(4-Methyl-1-piperazinyl)imino]methyl]rifamycin sv; 8-[[(4-Methylpiperazinyl)imino]methyl]rifamycin sv; 8CI)
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Indication
In total 1 Indication(s)
HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]
Approved
[1], [2]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (13 diseases)
Bacterial infection [ICD-11: 1A00-1C4Z]
[3], [4]
Helicobacter pylori infection [ICD-11: DA60]
[5]
HIV associated with tuberculosis [ICD-11: 1C60]
[6], [7], [8]
Hypothyroidism [ICD-11: 5A00]
[9]
Leprosy [ICD-11: 1B20]
[10]
Meningococcal disease [ICD-11: 1C1C]
[11]
Mycobacterial diseases [ICD-11: 1B2Z ]
[1], [2]
Nocardiosis [ICD-11: 1C1B]
[12]
Non-tuberculous mycobacteria infection [ICD-11: 1B21]
[13]
Staphylococcus meningitis [ICD-11: 1B54]
[14]
Tuberculosis [ICD-11: 1B10]
[15]
Tuberculous sclerokeratitis [ICD-11: 1B12]
[16]
Urinary tuberculosis [ICD-11: 1G80]
[17]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (2 diseases)
Bacterial infection [ICD-11: 1A00-1C4Z]
[18]
Clostridioides difficile intestinal infection [ICD-11: 1A04]
[19]
Target Bacterial RNA polymerase switch region (Bact RNAP-SR) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C43H58N4O12
IsoSMILES
C[C@H]1/C=C/C=C(\\C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)[C@](O4)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C)O)O)/C=N/N5CCN(CC5)C)/C
InChI
1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1
InChIKey
JQXXHWHPUNPDRT-WLSIYKJHSA-N
PubChem CID
135398735
ChEBI ID
CHEBI:28077
TTD Drug ID
D0G3DL
VARIDT ID
DR00196
INTEDE ID
DR1420
DrugBank ID
DB01045
Type(s) of Resistant Mechanism of This Drug
  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 Their Corresponding Diseases
ICD-01: Infectious/parasitic diseases
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Bacterial infection [ICD-11: 1A00-1C4Z]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Rifampin phosphotransferase (RPHB) [20]
Molecule Alteration Expression
Inherence
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Paenibacillus sp. LC231 1120679
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description RphB inactivates rifampin by Phosphorylation.
Key Molecule: rgt1438 (Unclear) [18]
Molecule Alteration Expression
Up-regulation
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Streptomyces albus J1074 457425
Streptomyces speibonae WAC1438 195801
Experiment for
Molecule Alteration
Whole genome sequence assay; Allelic frequency measurement assay
Experiment for
Drug Resistance
MIC assay
Mechanism Description Rgt1438R encode a rifampin-inactivating glycosyltransferase,as a rifampin resistance determinant from WAC1438 capable of inactivating an assortment of rifamycins.
Key Molecule: Rifampin monooxygenase (IRI) [21]
Molecule Alteration Expression
Inherence
Resistant Disease Rhodococcus equi infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli strain MM294 562
Rhodococcus equi strain ATCC 14887 43767
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
Monitored by zones of inhibition assay
Mechanism Description The original 8-kb clone and all subclones with the intact iri gene conferred similar 25-fold increases in rifampin resistance in rhodococcal strain Ri8. Clones growing on rifampin-containing selective plates all possessed an insert of about 8 kb, and retransformation into strain Ri8 demonstrated that this segment of DNA increased the rifampin MIC about 25-fold and conferred the ability to inactivate the antibiotic: rifampin at a concentration of 20 mg/ml was completely inactivated in about 6 h (as monitored by zones of inhibition on plates spread with a tester strain). inactivation gene cloned from the R.equi type strain, ATCC 14887, can confer a 10-fold increase in resistance to rifampin in E.coli as well as a 25-fold increase in Rhodococcus.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [3], [4]
Molecule Alteration Missense mutation
c.ins1593C
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli MG1655 511145
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Agar dilution method assay
Mechanism Description Frameshift mutations have been reported in rpoB, an essential gene encoding the beta-subunit of RNA polymerase, in rifampicin-resistant clinical isolates of Mycobacterium tuberculosis. Escherichia coli with a +1-nt frameshift mutation centrally located in rpoB is viable and highly resistant to rifampicin.
Clostridioides difficile intestinal infection [ICD-11: 1A04]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [19]
Molecule Alteration Mutation
p.R505K
Resistant Disease Clostridium difficile infection [ICD-11: 1A04.0]
Experimental Note Discovered Using In-vivo Testing Model
Mechanism Description RIFs (rifampicin and rifaximin) have recently been used as another option for CDI treatment. Nevertheless, the resistance to RIFs in C. difficile has been reported. These drugs target on a DNA-dependent RNA polymerase (RNAP), resulting in the extension of short transcript blockage. Point mutations within the rpoB gene encoding for beta-subunit of RNAP cause resistance to RIFs. Among identified amino acid substitutions, the R505K substitution has been mostly evident to promote the high level of resistance.
Tuberculosis [ICD-11: 1B10]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Enoyl-[acyl-carrier-protein] reductase [NADH] (INHA) [15]
Molecule Alteration Mutation
.
Resistant Disease Tuberculosis [ICD-11: 1B10.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis H37Rv 83332
Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
qRT-PCR
Mechanism Description Monoresistance to rifampicin and isoniazid was found in 11% (95% CI: 0.077-0.150; p, 0.087) and 8.5% (95% CI: 0.056-0.123; p, 0.692) of all the patients, respectively. Resistance to RIF and INH among newly diagnosed patients was 10.2% and 8.6%, while among previously treated patients, resistance to RIF and INH was 23.5% and 5.9% respectively. Furthermore, 4.9% of the samples from newly diagnosed with INH monoresistance, were found to have mutations in the InhA region while 8.6% had mutations in the katG region, a condition that can lead to phenotypic isoniazid drug resistance.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [15]
Molecule Alteration Mutation
.
Resistant Disease Tuberculosis [ICD-11: 1B10.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis H37Rv 83332
Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
qRT-PCR
Mechanism Description Monoresistance to rifampicin and isoniazid was found in 11% (95% CI: 0.077-0.150; p, 0.087) and 8.5% (95% CI: 0.056-0.123; p, 0.692) of all the patients, respectively. Resistance to RIF and INH among newly diagnosed patients was 10.2% and 8.6%, while among previously treated patients, resistance to RIF and INH was 23.5% and 5.9% respectively. Furthermore, 4.9% of the samples from newly diagnosed with INH monoresistance, were found to have mutations in the InhA region while 8.6% had mutations in the katG region, a condition that can lead to phenotypic isoniazid drug resistance.
Leprosy [ICD-11: 1B20]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Dihydrofolate reductase/DNA-directed RNA polymerase subunit beta (DHFR/RPOB) [10]
Molecule Alteration Missense mutation
folP p.P55L+poB p.S531L
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
Key Molecule: Dihydrofolate reductase/DNA-directed RNA polymerase subunit beta (DHFR/RPOB) [10]
Molecule Alteration Missense mutation
folP p.P55S+rpoB p.S531L+rpoB p.V547I
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
Key Molecule: Dihydrofolate reductase/DNA gyrase subunit A/DNA gyrase subunit B (DHFR/GYRA/GYRB) [10]
Molecule Alteration Missense mutation
folP p.P55L+gyrA p.A91V+gyrB p.A91V
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
Key Molecule: Dihydrofolate reductase/DNA gyrase subunit A/DNA gyrase subunit B (DHFR/GYRA/GYRB) [10]
Molecule Alteration Missense mutation
folP p.P55L+gyrA p.D205N+gyrB p.D205N
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Dihydrofolate reductase (DHFR) [10]
Molecule Alteration Missense mutation
p.T53A
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
Key Molecule: Dihydrofolate reductase (DHFR) [10]
Molecule Alteration Missense mutation
p.P55R
Resistant Disease Leprosy [ICD-11: 1B20.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium leprae isolates 1769
In Vivo Model Footpad granuloma from M. leprae-infected nude mice model Mus musculus
Experiment for
Molecule Alteration
PCR and single-stranded conformational polymorphism (SSCP) assay
Experiment for
Drug Resistance
Mouse footpad assay
Mechanism Description The mutations genes reported in this study have been demonstrated to be responsible for drug resistance by mouse footpad assay.
Mycobacterial diseases [ICD-11: 1B2Z ]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug efflux pump Tap (TAP) [1], [2]
Molecule Alteration Expression
Up-regulation
Resistant Disease Mycobacterium tuberculosis infection [ICD-11: 1B2Z.5]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis H37Rv 83332
Mycobacterium tuberculosis ICC154 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
MIC assay
Mechanism Description One mechanism proposed for drug resistance in Mycobacterium tuberculosis (MTB) is by efflux of the drugs by membrane located pumps.Mycobacterium tuberculosis isolate with a distinct genomic identity overexpresses a tap-like efflux pump,which confers resistance to Rifampin and Ofloxacin.
Key Molecule: Multidrug efflux pump Tap (TAP) [1], [2]
Molecule Alteration Expression
Up-regulation
Resistant Disease Mycobacterium fortuitum infection [ICD-11: 1B2Z.2]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis H37Rv 83332
Mycobacterium tuberculosis ICC154 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
MIC assay
Mechanism Description One mechanism proposed for drug resistance in Mycobacterium tuberculosis (MTB) is by efflux of the drugs by membrane located pumps.Mycobacterium tuberculosis isolate with a distinct genomic identity overexpresses a tap-like efflux pump,which confers resistance to Rifampin and Ofloxacin.
Staphylococcus meningitis [ICD-11: 1B54]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [14]
Molecule Alteration Missense mutation
p.H481N
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.A473T
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.Q465R
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.L466S
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.Q468K
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.D471Y
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.A477T
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.I527M
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.S529L
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.H481N+p.L466S
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.H481N+p.S529L
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.H481N+p.I527M
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.H481N+p.S529L+p.Q465R
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.H481N+p.A473T+p.A477T
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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) [14]
Molecule Alteration Missense mutation
p.D471Y+p.S486L
Resistant Disease Staphylococcus aureus infection [ICD-11: 1B54.0]
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.
Nocardiosis [ICD-11: 1C1B]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta 2 (RPOB2) [12]
Molecule Alteration Expression
Inherence
Resistant Disease Nocardiosis [ICD-11: 1C1B.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Nocardia farcinica IFM 10152 247156
Experiment for
Molecule Alteration
PCR; Southern analysis
Experiment for
Drug Resistance
Brain heart infusion (BHI) broth assay
Mechanism Description RpoB2 may have reduced binding affinity for RIF due to amino acid substitutions and is capable of functioning in the presence of RIF instead of RpoB. Besides, RNAP with RpoB2 may elicit expression of a latent RIF resistance gene which may be present in the genome.
HIV associated with tuberculosis [ICD-11: 1C60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Ribonuclease PH (RPH) [22], [23], [24]
Molecule Alteration Expression
Up-regulation
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Bacillus cereus RPH-Bc 1396
Escherichia coli Rosetta(DE3) pLysS 866768
L. monocytogenes 1639
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
MIC assay
Mechanism Description RIF phosphotransferase (rph) led to the identification of a new resistance gene and associated enzyme responsible for inactivating rifamycin antibiotics by phosphorylation.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.L511P
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.Q513P
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.Q513K
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.D516V
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526N+p.L533P
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526Y
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526R
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526D
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526N
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526L
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.H526C
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.S531W
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.S531L
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.L533P
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Missense mutation
p.E562G+p.P564L
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [6], [7], [8]
Molecule Alteration Frameshift mutation
c.513_516del*AA TTC ATG G*
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description More than 96% of rifampicin-resistant strains show mutations in a portion of the RNA polymerase B subunit gene (rpoB), called the hot-spot region, encompassing codons 507-533.Mutations L533P, H526L, D516Y and L511P and the double mutation E562G/P564L conferred a low level of resistance.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Uncharacterized MFS-type transporter EfpA (EFPA) [25], [26], [27]
Molecule Alteration Expression
Up-regulation
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis H37Rv 83332
Mycobacterium tuberculosis MTB1 1773
Mycobacterium tuberculosis MTB2 1773
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description The induced strains presented an increased efflux activity that was inhibited by the efflux inhibitors (EIs) and showed overexpression of the efflux pump genes efpA, mmpL7, mmr, p55 and the Tap-like gene Rv1258c. Altogether, these results correlate efflux activity with INH resistance and demonstrate that efflux pumps play an important role in acquired INH resistance in M. tuberculosis complex.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Probable arabinosyltransferase B (EMBB) [28]
Molecule Alteration Missense mutation
p.M306I
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
Test for drug susceptibility in L-J medium assay
Mechanism Description An embB mutation has a strong relationship to rifampin resistance. Inhibition of cell wall biosynthesis may not play an important role, and inhibition of RNA metabolism may be partly responsible.
Urinary tuberculosis [ICD-11: 1G80]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [17]
Molecule Alteration Missense mutation
p.S531L
Resistant Disease Urinary tuberculosis [ICD-11: 1G80.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Gene sequencing assay
Mechanism Description Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.
Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [17]
Molecule Alteration Missense mutation
p.S315T1
Resistant Disease Urinary tuberculosis [ICD-11: 1G80.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Gene sequencing assay
Mechanism Description Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Catalase-peroxidase (KATG) [17]
Molecule Alteration Missense mutation
p.S531L
Resistant Disease Urinary tuberculosis [ICD-11: 1G80.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Gene sequencing assay
Mechanism Description Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.
Key Molecule: Catalase-peroxidase (KATG) [17]
Molecule Alteration Missense mutation
p.S315T1
Resistant Disease Urinary tuberculosis [ICD-11: 1G80.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Mycobacterium tuberculosis isolates 1773
Experiment for
Molecule Alteration
Gene sequencing assay
Mechanism Description Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L.
References
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Ref 9 Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad DistrictIndian J Tuberc. 2021 Jul;68(3):379-383. doi: 10.1016/j.ijtb.2020.12.008. Epub 2021 Jan 4.
Ref 10 Mutations in genes related to drug resistance in Mycobacterium leprae isolates from leprosy patients in Korea. J Infect. 2005 Jan;50(1):6-11. doi: 10.1016/j.jinf.2004.03.012.
Ref 11 Antibiotics for preventing meningococcal infections .Cochrane Database Syst Rev. 2013 Oct 25;2013(10):CD004785. doi: 10.1002/14651858.CD004785.pub5. 10.1002/14651858.CD004785.pub5
Ref 12 Contribution of rpoB2 RNA polymerase beta subunit gene to rifampin resistance in Nocardia species. Antimicrob Agents Chemother. 2006 Apr;50(4):1342-6. doi: 10.1128/AAC.50.4.1342-1346.2006.
Ref 13 Comparison of Rifamycins for Efficacy Against Mycobacterium avium Complex and Resistance Emergence in the Hollow Fiber Model SystemFront Pharmacol. 2021 Apr 15;12:645264. doi: 10.3389/fphar.2021.645264. eCollection 2021.
Ref 14 Molecular characterization of rpoB mutations conferring cross-resistance to rifamycins on methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1999 Nov;43(11):2813-6. doi: 10.1128/AAC.43.11.2813.
Ref 15 Rifampicin and isoniazid drug resistance among patients diagnosed with pulmonary tuberculosis in southwestern Uganda .PLoS One. 2021 Oct 29;16(10):e0259221. doi: 10.1371/journal.pone.0259221. eCollection 2021. 10.1371/journal.pone.0259221
Ref 16 Tuberculous Scleritis and Multidrug ResistanceOcul Immunol Inflamm. 2021 Jan 8:1-10. doi: 10.1080/09273948.2020.1853176. Online ahead of print.
Ref 17 Clinical Features and Drug-Resistance Profile of Urinary Tuberculosis in South-Western China: A Cross-sectional Study .Medicine (Baltimore). 2016 May;95(19):e3537. doi: 10.1097/MD.0000000000003537. 10.1097/MD.0000000000003537
Ref 18 Characterization of a rifampin-inactivating glycosyltransferase from a screen of environmental actinomycetes. Antimicrob Agents Chemother. 2012 Oct;56(10):5061-9. doi: 10.1128/AAC.01166-12. Epub 2012 Jul 16.
Ref 19 Insights into drug resistance mechanisms in Clostridium difficile .Essays Biochem. 2017 Mar 3;61(1):81-88. doi: 10.1042/EBC20160062. Print 2017 Feb 28. 10.1042/EBC20160062
Ref 20 A diverse intrinsic antibiotic resistome from a cave bacterium. Nat Commun. 2016 Dec 8;7:13803. doi: 10.1038/ncomms13803.
Ref 21 Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob Agents Chemother. 1997 Jan;41(1):218-21. doi: 10.1128/AAC.41.1.218.
Ref 22 A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7102-7. doi: 10.1073/pnas.1402358111. Epub 2014 Apr 28.
Ref 23 Rifampin phosphotransferase is an unusual antibiotic resistance kinase. Nat Commun. 2016 Apr 22;7:11343. doi: 10.1038/ncomms11343.
Ref 24 Phosphorylative inactivation of rifampicin by Nocardia otitidiscaviarum. J Antimicrob Chemother. 1994 Jun;33(6):1127-35. doi: 10.1093/jac/33.6.1127.
Ref 25 Efflux pump-mediated intrinsic drug resistance in Mycobacterium smegmatis. Antimicrob Agents Chemother. 2004 Jul;48(7):2415-23. doi: 10.1128/AAC.48.7.2415-2423.2004.
Ref 26 Contribution of efflux activity to isoniazid resistance in the Mycobacterium tuberculosis complex. Infect Genet Evol. 2012 Jun;12(4):695-700. doi: 10.1016/j.meegid.2011.08.009. Epub 2011 Aug 17.
Ref 27 Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family. Clin Diagn Lab Immunol. 1997 Jan;4(1):23-32. doi: 10.1128/cdli.4.1.23-32.1997.
Ref 28 Lack of correlation between embB mutation and ethambutol MIC in Mycobacterium tuberculosis clinical isolates from China. Antimicrob Agents Chemother. 2007 Dec;51(12):4515-7. doi: 10.1128/AAC.00416-07. Epub 2007 Sep 10.

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