Role of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenes
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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”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [197]
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Metals in Motion: Understanding Labile Metal Pools in Bacteria
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Poly-Gamma-Glutamic Acid Secretion Protects Bacillus subtilis from Zinc and Copper Intoxication
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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.
- ORCID
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2020-12-22
- Volume
- 11
- Issue
- 6
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC7733945
- 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
- gold
- doi.org
- Licence
- 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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