Molecule Information

General Information of the Molecule (ID: Mol00801)

• Name: Aminoglycoside N(6')-acetyltransferase type 1 (A6AC1) ,Pseudomonas aeruginosa
• Synonyms: Aminoglycoside resistance protein
• Molecule Type: Protein
• Gene Name: aac(6')
• Sequence:
  MSKLGPTKPAPSMANTPVGNVVPCKTPDHPGWLELRLQLWPDGSTEEFLPEMAAACAEPD
  RFGQFLFLSPGGLAEGLVEVALRTDYVNGTESSPVAFLEGVFVVPASRGLGIARALVAAA
  EGWARDRGCTEFASDAEVSNVGSHAMHAALGFVETERVVFFRKVVAP
• Uniprot ID: S6CFI8_PSEAI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Pseudomonadales
Family: Pseudomonadaceae
Genus: Pseudomonas
Species: Pseudomonas aeruginosa

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Amikacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Amikacin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Arbekacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Arbekacin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Dibekacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Dibekacin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Isepamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Isepamicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Kanamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Kanamycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Sisomicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Sisomicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Tobramycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Tobramycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Disease Class: Bacterial infection [2], [3]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Tobramycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli JM83; 562
• In Vitro Model: Escherichia coli strain k802N; 562
• In Vitro Model: Pseudomonas aeruginosa strain BM2692; 287
• In Vitro Model: Pseudomonas aeruginosa strain BM2693; 287
• In Vitro Model: Pseudomonas aeruginosa strain BM2694; 287
• In Vitro Model: Pseudomonas aeruginosa strain BM2695; 287
• In Vitro Model: Pseudomonas fluorescens strain BM2687; 294
• In Vitro Model: Pseudomonas fluorescens strain BM2687-1; 294
• In Vitro Model: Pseudomonas fluorescens strain BM2687-2; 294
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: The aac(6')-Ib' gene from Pseudomonas fluorescens BM2687, encoding an aminoglycoside 6'-N-acetyltransferase type II which confers resistance to gentamicin but not to amikacin, was characterized.

References

• Ref 1: Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa. PLoS One. 2013 Aug 12;8(8):e70557. doi: 10.1371/journal.pone.0070557. eCollection 2013.
• Ref 2: Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycin treatment. J Infect Dis. 2000 Mar;181(3):1180-4. doi: 10.1086/315312.
• Ref 3: A spontaneous point mutation in the aac(6')-Ib' gene results in altered substrate specificity of aminoglycoside 6'-N-acetyltransferase of a Pseudomonas fluorescens strain. FEMS Microbiol Lett. 1994 Jan 15;115(2-3):297-304. doi: 10.1111/j.1574-6968.1994.tb06654.x.