Disease Information

General Information of the Disease (ID: DIS00128)

• Name: Respiratory trac infection
• ICD: ICD-11: CA45

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

Drug Resistance Data Categorized by Drug

Approved Drug(s) 14 drug(s) in total

Clindamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Clindamycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Dalfopristin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Dalfopristin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Dibekacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [2]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Dibekacin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Enoxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: DNA gyrase subunit A (GYRA) [3]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.G75S
• Resistant Drug: Enoxacin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Staphylococcus aureus isolates; 1280
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Quinolone/fluoroquinolone resistance is most likely due to mutations in the genes gyrA and parC encoding DNA gyrase and topoisomerase IV.

Key Molecule: DNA gyrase subunit A (GYRA) [3]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.S83R
• Resistant Drug: Enoxacin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Staphylococcus aureus isolates; 1280
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Quinolone/fluoroquinolone resistance is most likely due to mutations in the genes gyrA and parC encoding DNA gyrase and topoisomerase IV.

Gentamicin A

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [2]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Gentamicin A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Kanamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [2]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Kanamycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Lincomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Lincomycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Nalidixic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [3]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.S80L
• Resistant Drug: Nalidixic acid
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Pasteurella multocida 36950; 1075089
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Quinolone/fluoroquinolone resistance is most likely due to mutations in the genes gyrA and parC encoding DNA gyrase and topoisomerase IV.

Palivizumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.N262D
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.N268I
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272E
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272M
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272Q
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.S275F
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.S275L
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272N
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272T
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272M
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Key Molecule: Fusion glycoprotein F0 (F) [4]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Missense mutation; p.K272Q
• Resistant Drug: Palivizumab
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma haematobium strain; 6185
• Mechanism Description: Clinical isolates N262D, K272E/M/Q, and S275F/L were reported as possessing mutations in the F protein region palivizumab-binding site (amino acids 258-275) and exhibiting resistance to palivizumab neutralization, while laboratory induced isolates N268I, and K272N/T/M/Q have also been reported.

Sisomicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [2]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Sisomicin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Spectinomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Pasteurella multocida infection [ICD-11: 1B99.0]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Spectinomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Mannheimia haemolytica infection [ICD-11: CA45.3]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Spectinomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Histophilus somni infection [ICD-11: CA45.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Spectinomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Streptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Pasteurella multocida infection [ICD-11: 1B99.0]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Streptomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Mannheimia haemolytica infection [ICD-11: CA45.3]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Streptomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [5]

• Resistant Disease: Histophilus somni infection [ICD-11: CA45.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Streptomycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli JM109 cells; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AadA14 is the fifth reading frame in pCCk647 coded for a (3")(9) adenylyltransferase of 261 amino acids. The emergence of aada14 leads to drug resistance.

Tiamulin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Tiamulin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Tobramycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [2]

• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Tobramycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

References

• Ref 1: Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70. Antimicrob Agents Chemother. 2011 Apr;55(4):1470-4. doi: 10.1128/AAC.01068-10. Epub 2011 Jan 18.
• Ref 2: Novel aminoglycoside 2''-phosphotransferase identified in a gram-negative pathogen. Antimicrob Agents Chemother. 2013 Jan;57(1):452-7. doi: 10.1128/AAC.02049-12. Epub 2012 Nov 5.
• Ref 3: Topoisomerase mutations that are associated with high-level resistance to earlier fluoroquinolones in Staphylococcus aureus have less effect on the antibacterial activity of besifloxacin. Chemotherapy. 2011;57(5):363-71. doi: 10.1159/000330858. Epub 2011 Oct 12.
• Ref 4: Neutralizing epitopes of RSV and palivizumab resistance in Japan .Fukushima J Med Sci. 2017 Dec 19;63(3):127-134. doi: 10.5387/fms.2017-09. Epub 2017 Sep 1. 10.5387/fms.2017-09
• Ref 5: Novel spectinomycin/streptomycin resistance gene, aadA14, from Pasteurella multocida. Antimicrob Agents Chemother. 2005 Jul;49(7):3046-9. doi: 10.1128/AAC.49.7.3046-3049.2005.