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 K. Waters, Ashley B. Carey, Alex Ashenden, Kimberley T. McLean, Erin B. Brazel, Jhih-Hang Jiang, Alessandra Panizza, Claudia Trappetti, James C. Paton, Anton Y. Peleg, Ingo Köper, Ian T. Paulsen, Karl A. Hassan, Megan L. O'Mara, Bart A. Eijkelkamp*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)
    7 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)1-6
    Number of pages6
    JournalmBio
    Volume12
    Issue number3
    DOIs
    Publication statusPublished - Jun 2021

    Bibliographical note

    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • bacterial
    • host lipids
    • antibiotics
    • resistance
    • RND efflux
    • Resistance
    • Bacterial
    • Host lipids
    • Antibiotics

    Fingerprint

    Dive into the research topics of 'The membrane composition defines the spatial organization and function of a major <i>Acinetobacter baumannii</i> drug efflux system'. Together they form a unique fingerprint.

    Cite this