The role of the copA copper efflux system in acinetobacter baumannii virulence

Saleh F. Alquethamy, Marjan Khorvash, Victoria G. Pederick, Jonathan J. Whittall, James C. Paton, Ian T. Paulsen, Karl A. Hassan, Christopher A. McDevitt, Bart A. Eijkelkamp

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Abstract

Acinetobacter baumannii has emerged as one of the leading causative agents of nosocomial infections. Due to its high level of intrinsic and adapted antibiotic resistance, treatment failure rates are high, which allows this opportunistic pathogen to thrive during infection in immune-compromised patients. A. baumannii can cause infections within a broad range of host niches, with pneumonia and bacteraemia being associated with the greatest levels of morbidity and mortality. Although its resistance to antibiotics is widely studied, our understanding of the mechanisms required for dealing with environmental stresses related to virulence and hospital persistence, such as copper toxicity, is limited. Here, we performed an in silico analysis of the A. baumannii copper resistome, examining its regulation under copper stress. Using comparative analyses of bacterial P-type ATPases, we propose that A. baumannii encodes a member of a novel subgroup of P 1B-1 ATPases. Analyses of three putative inner membrane copper efflux systems identified the P 1B-1 ATPase CopA as the primary mediator of cytoplasmic copper resistance in A. baumannii. Using a murine model of A. baumannii pneumonia, we reveal that CopA contributes to the virulence of A. baumannii. Collectively, this study advances our understanding of how A. baumannii deals with environmental copper toxicity, and it provides novel insights into how A. baumannii combats adversities encountered as part of the host immune defence.

Original languageEnglish
Article number575
JournalInternational Journal of Molecular Sciences
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Feb 2019
Externally publishedYes

Bibliographical note

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • Bacterial
  • Metal ions
  • P-type ATPases
  • Virulence

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