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Phenotype microarray analysis of the AdeRS two-component system in Acinetobacter baumannii.

J-R Sun1, Y-S Chiang2,3, H-S Shang1

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European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology
|July 26, 2017
PubMed
Summary
This summary is machine-generated.

The AdeRS two-component system (TCS) in Acinetobacter baumannii controls antibiotic resistance by managing the AdeABC efflux pump. Deleting AdeRS increases sensitivity to certain antibiotics, highlighting its role in antimicrobial resistance.

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Acinetobacter baumannii is a significant nosocomial pathogen known for its multidrug resistance.
  • The AdeRS two-component system (TCS) regulates the AdeABC efflux pump, a key factor in antimicrobial resistance.

Purpose of the Study:

  • To investigate the role of the AdeRS TCS in Acinetobacter baumannii's antimicrobial resistance mechanisms.
  • To characterize the impact of AdeRS deletion on bacterial tolerance to various compounds.

Main Methods:

  • Construction and characterization of an Acinetobacter baumannii mutant lacking the AdeRS TCS.
  • Phenotype microarray (PM) analysis to assess compound tolerance.
  • Complementation studies to validate AdeRS function.
  • Minimum inhibitory concentration (MIC) determination and spot assays for phleomycin sensitivity.

Main Results:

  • The AdeRS deletion mutant exhibited reduced expression of the AdeABC efflux pump.
  • Significant differences in tolerance to 91 compounds were observed between the mutant and parental strains.
  • The AdeRS deletion strain showed increased sensitivity to inhibitors targeting protein synthesis and cell membrane permeability.
  • Phleomycin tolerance was significantly reduced in the AdeRS deletion strain, and this could be restored by complementation.
  • An efflux pump inhibitor (NMP) reduced phleomycin MIC in a substantial portion of clinical isolates.

Conclusions:

  • The AdeRS TCS is crucial for Acinetobacter baumannii's ability to eliminate antibiotics and tolerate specific compounds.
  • Targeting the AdeRS system or its associated efflux pump may offer strategies to combat multidrug-resistant Acinetobacter baumannii infections.