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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
1Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Summary
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.
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.
