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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

882

Aminoglycoside 6'-N-acetyltransferase Type Ib [AAC(6')-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion

Craig M Reeves1, Jesus Magallon1, Kenneth Rocha1

  • 1Center for Applied Biotechnology Studies, Department of Biological Science, California State University Fullerton, Fullerton, CA 92831, USA.

Antibiotics (Basel, Switzerland)
|January 5, 2021
PubMed

Insights

Silver acetate effectively inhibits aminoglycoside resistance enzymes, restoring amikacin

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Clinical resistance to aminoglycosides like amikacin is often caused by the enzyme aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib].
  • AAC(6')-Ib inactivates aminoglycosides via acetylation, contributing to bacterial resistance.
  • Combining antibiotics with enzyme inhibitors is a potential strategy to overcome antimicrobial resistance.

Purpose of the Study:

  • To investigate silver acetate as an inhibitor of AAC(6')-Ib-mediated aminoglycoside inactivation.
  • To evaluate the efficacy of silver acetate in combination with amikacin against resistant bacteria.
  • To explore the mechanism of action for silver ion potentiation of aminoglycoside activity.

Main Methods:

  • In vitro enzymatic assays to assess silver acetate's inhibition of AAC(6')-Ib.
  • Bacterial culture experiments with amikacin-resistant *Acinetobacter baumannii* and *Escherichia coli* treated with silver acetate and amikacin.
  • Time-kill assays and cytotoxicity assessments using HEK293 cells.

Main Results:

  • Silver acetate robustly inhibited AAC(6')-Ib enzymatic activity in vitro.
  • Co-administration of silver acetate and amikacin significantly reduced resistance levels in *A. baumannii* and *E. coli*.
  • The combination demonstrated bactericidal activity with low cytotoxicity to human cells.

Conclusions:

  • Silver acetate is a potent inhibitor of AAC(6')-Ib, offering a novel approach to combat aminoglycoside resistance.
  • The combination therapy of silver acetate and amikacin shows promise for treating infections caused by resistant Gram-negative bacteria.
  • Silver acetate's inhibitory effect on AAC(6')-Ib appears independent of ROS generation or membrane permeability changes.
Keywords:
AcinetobacterESKAPEacetyltransferaseadjuvantamikacinaminoglycosidessilver

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