Molecule Information

General Information of the Molecule (ID: Mol04286)

• Name: Aminoglycoside 2'-N-acetyltransferase type IA [AAC(2')-IA] ,Escherichia coli
• Synonyms: Aminoglycoside 2'-N-acetyltransferase type IA [AAC(2')-IA]
• Molecule Type: Protein

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Plazomicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Escherichia coli infection [ICD-11: 1A03.0] [1]

• Sensitive Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Sensitive Drug: Plazomicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Acetyltransferase assay
• Experiment for Drug Resistance: Time-Kill assay; Cytotoxicity assay
• Mechanism Description: Plazomicin is a recent U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6' position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2'-N-acetyltransferase type Ia [AAC(2')-Ia], which reduces the antibiotic's potency. Silver acetate is a potent inhibitor of AAC(2')-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2')-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

References

• Ref 1: Inhibition of Enzymatic Acetylation-Mediated Resistance to Plazomicin by Silver Ions. Pharmaceuticals (Basel). 2023 Feb 3;16(2):236.