The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump

Francesca L. Short; Qi Liu; Bhumika Shah; Heather E. Clift; Varsha Naidu; Liping Li; Farzana T. Prity; Bridget C. Mabbutt; Karl A. Hassan; Ian T. Paulsen

doi:10.1038/s42003-021-02629-6

The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump

Francesca L. Short, Qi Liu, Bhumika Shah, Heather E. Clift, Varsha Naidu, Liping Li, Farzana T. Prity, Bridget C. Mabbutt, Karl A. Hassan, Ian T. Paulsen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

123 Downloads (Pure)

Abstract

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.

Original language	English
Article number	1114
Pages (from-to)	1-12
Number of pages	12
Journal	Communications Biology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s42003-021-02629-6
Publication status	Published - 22 Sept 2021

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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.

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10.1038/s42003-021-02629-6

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Cite this

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title = "The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump",

abstract = "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.",

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doi = "10.1038/s42003-021-02629-6",

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AU - Short, Francesca L.

AU - Liu, Qi

AU - Shah, Bhumika

AU - Clift, Heather E.

AU - Naidu, Varsha

AU - Li, Liping

AU - Prity, Farzana T.

AU - Mabbutt, Bridget C.

AU - Hassan, Karl A.

AU - Paulsen, Ian T.

N1 - 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.

PY - 2021/9/22

Y1 - 2021/9/22

N2 - 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.

AB - 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.

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The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump

Abstract

Bibliographical note

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Other files and links

Fingerprint

Circuit Breaker: Investigating the regulatory circuits controlling expression of drug efflux pumps in the nosocomial pathogen Acinetobacter baumannii

DECRA: Taking control: Uncovering the regulatory networks for bacterial iron acquisition

X-ray facility for protein crystallography

Cite this

The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Projects

Circuit Breaker: Investigating the regulatory circuits controlling expression of drug efflux pumps in the nosocomial pathogen Acinetobacter baumannii

DECRA: Taking control: Uncovering the regulatory networks for bacterial iron acquisition

X-ray facility for protein crystallography

Cite this