Publication Date:
2022-05-26
Description:
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Tarrant, E., P Riboldi, G., McIlvin, M. R., Stevenson, J., Barwinska-Sendra, A., Stewart, L. J., Saito, M. A., & Waldron, K. J. Copper stress in staphylococcus aureus leads to adaptive changes in central carbon metabolism. Metallomics, 11, (2019): 183-200, doi: 10.1039/C8MT00239H.
Description:
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.
Description:
KJW and ET were supported by a Sir Henry Dale Fellowship (to KJW) funded by the Wellcome Trust and the Royal Society (098375/Z/12/Z), and GPR was funded by a CAPES Science Without Borders scholarship (BEX 2445/13-1). JS (BB/F015895/1) and ABS (BB/J014516/1) were supported by BBSRC PhD studentships, and LS was supported by a Newcastle University Research Excellence Academy PhD studentship (05MREA). MAS was supported by the Gordon and Betty Moore Foundation Grant (GBM3782). We also thank Prof. Simon Foster (Sheffield, UK) for the gift of S. aureus strain SH1000, and Dr Julie Morrissey (Leicester, UK) for phage φ11.
Repository Name:
Woods Hole Open Access Server
Type:
Article
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