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

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

doi:10.1038/s42003-021-02629-6

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.

Highlights

Antimicrobial resistance genes, including multidrug efflux pumps, evolved long before the ubiquitous use of antimicrobials in medicine and infection control
A. baumannii has a particular ability to survive for prolonged times in hospital environments[11], and this is due in part to high disinfectant tolerance conferred by its repertoire of MDEPs11,12
We have investigated the transcriptomic response of A. baumannii to high levels of the four major biological polyamines, with a view to defining their physiological roles and identifying transporters responsible for efflux of these molecules

Summary

Introduction

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. Multidrug efflux pumps (MDEPs) are an important category of AMR determinant, and often have core physiological functions[6,7]. These functions broadly fall into removal of harmful exogenous molecules (for example, mammalian antimicrobial peptides or plant flavonoids) or secretion of endogenous molecules (such as siderophores, quorum-sensing signals or metabolites)[2,6,7]. It was shown that the physiological substrates of AceI—a chlorhexidine efflux pump encoded in the core genome of A. baumannii15,17—are likely to be short-chain polyamines[18]

Methods

Results

Conclusion