The Membrane Composition Defines the Spatial Organization and Function of a Major Acinetobacter baumannii Drug Efflux System

Maoge Zang, Hugo MacDermott-Opeskin, Felise G. Adams, Varsha Naidu, Jack Waters, Ashley B Carey, Alex Ashenden, Kimberley McLean, Erin B. Brazel, Jhih Hang Jiang, Alessandra Panizza, Claudia Trappetti, James C Paton, Anton Pelag, Ingo Köper, Ian T Paulsen, Karl A. Hassan, Megan L. O'Mara, Bart A Eijkelkamp

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
30 Downloads (Pure)

Abstract

Acinetobacter baumannii is one of the world’s most problematic nosocomial pathogens. The combination of its intrinsic resistance and ability to acquire resistance markers allow this organism to adjust to antibiotic treatment. Despite being the primary barrier against antibiotic stress, our understanding of the A. baumannii membrane composition and its impact on resistance remains limited. In this study, we explored how the incorporation of host-derived polyunsaturated fatty acids (PUFAs) is associated with increased antibiotic susceptibility. Functional analyses of primary A. baumannii efflux systems indicated that AdeB-mediated antibiotic resistance was impacted by PUFA treatment. Molecular dynamics simulations of AdeB identified a specific morphological disruption of AdeB when positioned in the PUFA-enriched membrane. Collectively, we have shown that PUFAs can impact antibiotic efficacy via a vital relationship with antibiotic efflux pumps. Furthermore, this work has revealed that A. baumannii’s unconditional desire for fatty acids may present a possible weakness in its multidrug resistance capacity.
Original languageEnglish
Article numbere01070-21
Pages (from-to) e01070-21
Number of pages6
JournalmBio
Volume12
Issue number3
DOIs
Publication statusPublished - 29 Jun 2021

Keywords

  • antibiotics
  • bacterial
  • host lipids
  • resistance
  • RND efflux

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