Projects per year
Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control. Multidrug efflux pumps often transport metabolites, signals and host-derived molecules in addition to antibiotics or biocides. Understanding their ancestral physiological roles could inform the development of strategies to subvert their activity. In this study, we investigated the response of Acinetobacter baumannii to polyamines, a widespread, abundant class of amino acid-derived metabolites, which led us to identify long-chain polyamines as natural substrates of the disinfectant efflux pump AmvA. Loss of amvA dramatically reduced tolerance to long-chain polyamines, and these molecules induce expression of amvA through binding to its cognate regulator AmvR. A second clinically-important efflux pump, AdeABC, also contributed to polyamine tolerance. Our results suggest that the disinfectant resistance capability that allows A. baumannii to survive in hospitals may have evolutionary origins in the transport of polyamine metabolites.
|Number of pages||12|
|Publication status||Published - 22 Sep 2021|
Bibliographical noteCopyright 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.
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DECRA: Taking control: Uncovering the regulatory networks for bacterial iron acquisition
3/06/20 → 2/06/23
Circuit Breaker: Investigating the regulatory circuits controlling expression of drug efflux pumps in the nosocomial pathogen Acinetobacter baumannii
Paulsen, I., Hassan, K., Cain, A. & Elbourne, L.
1/01/17 → …
X-ray facility for protein crystallography
Curmi, P., Jacques, D., Ryan, R. M., Mackay, J. P., Mabbutt, B., Paulsen, I., Duggin, I., Harry, E., Oakley, A. & Dixon, N. E.
8/05/19 → 31/12/19