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A horizontally gene transferred copper resistance locus confers hyper‐resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages

Lookup NU author(s): Dr Emma Tarrant, Dr Kevin WaldronORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd. Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) USA300, confers copper hyper-resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B-3-ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper-resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity.

Publication metadata

Author(s): Purves J, Thomas J, Riboldi GP, Zapotoczna M, Tarrant E, Andrew PW, Londono A, Planet PJ, Geoghegan JA, Waldron KJ, Morrissey JA

Publication type: Article

Publication status: Published

Journal: Environmental Microbiology

Year: 2018

Volume: 20

Issue: 4

Pages: 1576-1589

Print publication date: 01/04/2018

Online publication date: 26/03/2018

Acceptance date: 27/02/2018

Date deposited: 10/04/2018

ISSN (print): 1462-2912

ISSN (electronic): 1462-2920

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/1462-2920.14088

DOI: 10.1111/1462-2920.14088

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