Cited by 72Bacterial Genetics and BiotechnologyRedox biology and oxidative stressTrace Elements in Health

Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes

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Stewart, Louisa J., Ong, Cheryl-lynn Y., Zhang, May M., Brouwer, Stephan, McIntyre, Liam, Davies, Mark R., Walker, Mark J., McEwan, Alastair G. +2 more·2020·mBio

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Abstract

The control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it has been established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity. Glutathione, abundant in many bacteria, is known to bind Cu and has long been assumed to contribute to bacterial Cu handling. However, there is some ambiguity since neither its biosynthesis nor uptake is Cu-regulated. Furthermore, there is little experimental support for this physiological role of glutathione beyond measuring growth of glutathione-deficient mutants in the presence of Cu. Our work with group A Streptococcus provides new evidence that glutathione increases the threshold of intracellular Cu availability that can be tolerated by bacteria and thus advances fundamental understanding of bacterial Cu handling.

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  • LMW thiols GSH and BSH are implicated in cytosolic trafficking of both zinc and copper.

    “Similarly, the LMW thiols GSH and BSH are implicated in cytosolic trafficking of both zinc167,184 and copper197”

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Authors
Stewart, L. J., Ong, C.-L. Y., Zhang, M. M., Brouwer, S., McIntyre, L., Davies, M. R., Walker, M. J., McEwan, A. G., Waldron, K. J., & Djoko, K. Y.
Affiliations
  • Durham University (GB)
  • The University of Queensland (AU)
  • The University of Melbourne (AU)
  • Newcastle University (GB)
Corresponding author
Djoko, Karrera Y.
Venue
mBio
Published
2020-12-22
Volume
11
Issue
6
ISSN
  • 2150-7511 (ISSN-L)
  • 2161-2129
OpenAlex
W3109532390
Cited by
72
References
8
Citations by year
2026: 7 · 2025: 15 · 2024: 9 · 2023: 17 · 2022: 12 · 2021: 10 · 2020: 2
FWCI
5.92
Type
journal article
Language
en
Open access
Locations
  • mBio (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Royal Society (Research Grant RSG\R1\180044)
  • Garnett Passe and Rodney Williams Memorial Foundation (Research Fellowship)
  • UKRI | Biotechnology and Biological Sciences Research Council (BB/S006818/1)
  • Department of Health, Australian Government | National Health and Medical Research Council
  • Wellcome (Seed Award 214930/Z/18/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
glutathione, copper homeostasis, Streptococcus pyogenes, intracellular copper, metal sensing
MeSH terms
Animals, Bacterial Proteins, Biological Transport, Copper, Cytoplasm, Disease Models, Animal, Energy Metabolism, Glutathione, Homeostasis, Mutation, Streptococcal Infections, Streptococcus pyogenes, Stress, Physiological, Virulence, Gene Expression Regulation, Bacterial, Biofilms, Mice

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