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Polymyxin Resistance in Acinetobacter baumannii: Genetic Mutations and Transcriptomic Changes in Response to

Soon-Ee Cheah1, Matthew D Johnson1, Yan Zhu1

  • 1Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.

Scientific Reports
|May 20, 2016
PubMed

Insights

Polymyxin resistance in A. baumannii emerges rapidly, often linked to pmrB mutations. While some resistance reverses, understanding these mechanisms is crucial for developing new combination therapies against multidrug-resistant infections.

Area of Science:

  • Microbiology
  • Genomics
  • Pharmacodynamics

Background:

  • Polymyxins are critical last-line antibiotics for treating multidrug-resistant Acinetobacter baumannii infections.
  • Emerging polymyxin resistance in A. baumannii necessitates urgent investigation into resistance mechanisms.

Purpose of the Study:

  • To investigate the genomic and transcriptomic mechanisms of polymyxin resistance in A. baumannii.
  • To evaluate polymyxin B and colistin efficacy and resistance development under clinically relevant in vitro conditions.

Main Methods:

  • Genomic and transcriptomic analyses of A. baumannii exposed to polymyxin B and colistin in a dynamic in vitro model over 96 hours.
  • Evaluation of bacterial killing, resistance development, and reversion to susceptibility during drug-free passaging.

Main Results:

  • Polymyxin B achieved significant bacterial killing at high peak concentrations, while colistin showed limited efficacy.
  • Polymyxin resistance developed across all tested regimens, with stable resistance associated with pmrB mutations.
  • Altered expression of outer membrane biogenesis genes was observed in resistant strains, with partial reversion to susceptibility noted in some samples.

Conclusions:

  • Polymyxin resistance in A. baumannii can develop rapidly and is associated with specific genetic mutations (pmrB) and outer membrane alterations.
  • Understanding these resistance mechanisms is vital for developing effective therapeutic strategies, including combination therapies.

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