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Copper stress in Staphylococcus aureus leads to adaptive changes in central carbon metabolism

Lookup NU author(s): Dr Emma Tarrant, Jack Stevenson, Dr Anna Barwinska-Sendra, Louisa Stewart, Dr Kevin Waldron

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


Abstract

Copper toxicity has been a long-term selection pressure on bacteria due to its presence in the environment and its use as an antimicrobial agent by grazing protozoa, by phagocytic cells of the immune system, and in man-made medical and commercial products. There is recent evidence that exposure to increased copper stress may have been a key driver in the evolution and spread of methicillin-resistant Staphylococcus aureus, a globally important pathogen that causes significant mortality and morbidity worldwide. Yet it is unclear how S. aureus physiology is affected by copper stress or how it adapts in order to be able to grow in the presence of excess copper. Here, we have determined quantitatively how S. aureus alters its proteome during growth under copper stress conditions, comparing this adaptive response in two different types of growth regime. We found that the adaptive response involves induction of the conserved copper detoxification system as well as induction of enzymes of central carbon metabolism, with only limited induction of proteins involved in the oxidative stress response. Further, we identified a protein that binds copper inside S. aureus cells when stressed by copper excess. This copper-binding enzyme, a glyceraldehyde-3-phosphate dehydrogenase essential for glycolysis, is inhibited by copper in vitro and inside S. aureus cells. Together, our data demonstrate that copper stress leads to the inhibition of glycolysis in S. aureus, and that the bacterium adapts to this stress by altering its central carbon utilisation pathways


Publication metadata

Author(s): Tarrant E, Riboldi GP, McIlvin MR, Stevenson J, Barwinska-Sendra A, Stewart LJ, Saitob MA, Waldron KJ

Publication type: Article

Publication status: Published

Journal: Metallomics

Year: 2019

Volume: 11

Issue: 1

Pages: 183-200

Print publication date: 01/01/2019

Online publication date: 16/11/2018

Acceptance date: 19/10/2018

Date deposited: 20/12/2018

ISSN (print): 1756-5901

ISSN (electronic): 1756-591X

Publisher: Royal Society of Chemistry

URL: https://doi.org/10.1039/C8MT00239H

DOI: 10.1039/C8MT00239H


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