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Volume 20
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10.3390/ijms20030575
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Article

The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence

by
Saleh F. Alquethamy
1,2,
Marjan Khorvash
1,
Victoria G. Pederick
1,
Jonathan J. Whittall
1,3,
James C. Paton
1,
Ian T. Paulsen
4,
Karl A. Hassan
5,
Christopher A. McDevitt
2,* and
Bart A. Eijkelkamp
1,*
1
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide 5005, South Australia, Australia
2
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3000, Victoria, Australia
3
School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide 5001, South Australia, Australia
4
Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney 2109, New South Wales, Australia
5
School of Environmental and Life Sciences, University of Newcastle, Callaghan 2308, New South Wales, Australia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 575; https://doi.org/10.3390/ijms20030575
Received: 18 January 2019 / Revised: 25 January 2019 / Accepted: 26 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue Copper in Biology: Maturation of Copper Proteins and Copper Homeostasis)
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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 P1B-1 ATPases. Analyses of three putative inner membrane copper efflux systems identified the P1B-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. View Full-Text
Keywords: bacterial; metal ions; P1B-1; P-type ATPases; virulence bacterial; metal ions; P1B-1; P-type ATPases; virulence
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MDPI and ACS Style

Alquethamy, S.F.; Khorvash, M.; Pederick, V.G.; Whittall, J.J.; Paton, J.C.; Paulsen, I.T.; Hassan, K.A.; McDevitt, C.A.; Eijkelkamp, B.A. The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence. Int. J. Mol. Sci. 2019, 20, 575. https://doi.org/10.3390/ijms20030575

AMA Style

Alquethamy SF, Khorvash M, Pederick VG, Whittall JJ, Paton JC, Paulsen IT, Hassan KA, McDevitt CA, Eijkelkamp BA. The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence. International Journal of Molecular Sciences. 2019; 20(3):575. https://doi.org/10.3390/ijms20030575

Chicago/Turabian Style

Alquethamy, Saleh F., Marjan Khorvash, Victoria G. Pederick, Jonathan J. Whittall, James C. Paton, Ian T. Paulsen, Karl A. Hassan, Christopher A. McDevitt, and Bart A. Eijkelkamp 2019. "The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence" International Journal of Molecular Sciences 20, no. 3: 575. https://doi.org/10.3390/ijms20030575

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