Academic Journal
Zinc tolerance through glutathione import strikes a fine balance between protection and damage in Streptococcus mutans.
| Τίτλος: | Zinc tolerance through glutathione import strikes a fine balance between protection and damage in Streptococcus mutans. |
|---|---|
| Συγγραφείς: | Carter MC; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA., Womack E; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA., Khatib M; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA., Peterson AM; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA., Saengpet IS; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA., Lemos JA; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA. |
| Πηγή: | Microbiology (Reading, England) [Microbiology (Reading)] 2026 Aug; Vol. 172 (8). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Microbiology Society Country of Publication: England NLM ID: 9430468 Publication Model: Print Cited Medium: Internet ISSN: 1465-2080 (Electronic) Linking ISSN: 13500872 NLM ISO Abbreviation: Microbiology (Reading) Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : London : Microbiology Society Original Publication: Reading, U.K. : Society for General Microbiology, c1994- |
| Ιατρικοί όροι (MeSH): | Glutathione*/metabolism , Streptococcus mutans*/metabolism , Streptococcus mutans*/genetics , Streptococcus mutans*/drug effects , Streptococcus mutans*/growth & development , Zinc*/metabolism , Zinc*/toxicity, Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Gene Deletion ; Stress, Physiological ; Biological Transport |
| Περίληψη: | Recently, our group showed that the dental pathogen Streptococcus mutans is inherently more tolerant to high zinc stress than other streptococci, a phenotype associated with the presence of a P-type ATPase exporter named ZccE, virtually unique to S. mutans. In addition to zccE, a previous transcriptome analysis revealed that S. mutans upregulates genes involved in glutathione uptake during initial exposure to zinc stress. Glutathione, a major supplier of organic sulphur that also plays key roles in antioxidant defence and xenobiotic detoxification, forms coordination complexes with a variety of metals, including zinc, thereby functioning as a buffer that protects cells from metal intoxication. To investigate the contribution of glutathione zinc tolerance in S. mutans, the gshT gene, which encodes the substrate-binding subunit of a glutathione transporter, was deleted in both the parent and ΔzccE strains, and the ability of these mutants to overcome zinc stress through intracellular glutathione accumulation was determined. Targeted metabolomics revealed that S. mutans accumulates glutathione in a GshT-dependent manner following zinc stress, a response that was strikingly amplified in the ΔzccE strain. Although glutathione supplementation had a minimal impact on the growth of either parent or mutant strains in sub-inhibitory zinc concentrations, the ΔgshT strain exhibited increased zinc sensitivity in a plate-based assay. However, the ΔzccEΔgshT mutant displayed enhanced zinc tolerance compared to the ΔzccE single mutant. While glutathione alone did not alter zinc levels in the UA159 or ΔzccE strains, the combination of zinc and glutathione nearly doubled intracellular zinc levels in ΔzccE compared to cells grown in zinc only. We conclude that while glutathione may play a minor role in S. mutans zinc tolerance, enhanced glutathione uptake observed in ΔzccE facilitates zinc entry, as glutathione:Zn2+ complexes inadvertently promote zinc intoxication via a Trojan horse mechanism. |
| Σχόλια: | Update of: bioRxiv. 2026 Jun 02:2026.06.01.728743. doi: 10.64898/2026.06.01.728743.. (PMID: 42282517) |
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| Grant Information: | F31 DE032899 United States DE NIDCR NIH HHS; R01 DE032555 United States DE NIDCR NIH HHS; T90 DE021990 United States DE NIDCR NIH HHS |
| Contributed Indexing: | Keywords: Streptococcus mutans; ZccE; glutathione; metal stress; zinc mismetallation |
| Substance Nomenclature: | GAN16C9B8O (Glutathione) J41CSQ7QDS (Zinc) 0 (Bacterial Proteins) 0 (glutathione transporter) 0 (Membrane Transport Proteins) |
| Entry Date(s): | Date Created: 20260810 Date Completed: 20260810 Latest Revision: 20260826 |
| Update Code: | 20260826 |
| PubMed Central ID: | PMC13456638 |
| DOI: | 10.1099/mic.0.001754 |
| PMID: | 42574064 |
| Βάση Δεδομένων: | MEDLINE |
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