Academic Journal
Quorum sensing rewires membrane vesicle protein cargo to promote antibiotic persistence in Streptococcus mutans.
| Τίτλος: | Quorum sensing rewires membrane vesicle protein cargo to promote antibiotic persistence in Streptococcus mutans. |
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| Συγγραφείς: | Dufour D; Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada., Leiva-Sabadini C; Institute for Biological and Medical Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile., Aguayo S; Institute for Biological and Medical Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile.; School of Dentistry, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile., Lévesque CM; Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. |
| Πηγή: | Journal of bacteriology [J Bacteriol] 2026 Aug 20; Vol. 208 (8), pp. e0032326. Date of Electronic Publication: 2026 Jul 14. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 2985120R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5530 (Electronic) Linking ISSN: 00219193 NLM ISO Abbreviation: J Bacteriol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Quorum Sensing*/physiology , Streptococcus mutans*/drug effects , Streptococcus mutans*/physiology , Streptococcus mutans*/genetics , Streptococcus mutans*/metabolism , Anti-Bacterial Agents*/pharmacology , Bacterial Proteins*/metabolism , Bacterial Proteins*/genetics , Membrane Proteins*/metabolism |
| Περίληψη: | Quorum sensing (QS) plays a central role in the adaptive biology of Streptococcus mutans, yet the extent to which competence-stimulating peptide (CSP) signaling intersects with membrane vesicle production and function remained unclear. In this study, CSP activation markedly increased membrane vesicle output during the stationary phase and drove extensive changes in vesicle protein composition. Proteomic analysis revealed broad remodeling of vesicle cargo, including shifts in subcellular origin, and enrichment of multiple functional protein classes. Notably, CSP-induced vesicles carried the persistence-associated peptide Pep299, suggesting a link between QS-dependent cargo loading and antibiotic survival. To examine the functional consequences of this remodeling, S. mutans cells were pre-exposed to vesicles prior to antibiotic challenge. Vesicles derived from CSP-induced cultures promoted persister formation in a concentration-dependent manner, whereas vesicles from non-induced cultures exhibited minimal activity. Wild-type vesicles increased persistence, and vesicles from Pep299-overexpressing cells further enhanced this phenotype at lower vesicle concentrations. In contrast, vesicles derived from a Δ299 mutant failed to promote persistence, demonstrating that Pep299 is a key determinant of this activity. At higher vesicle abundance, the responses of wild-type and Pep299-enriched vesicles converged, consistent with endogenous CSP-dependent Pep299 loading. Fusion assays using R18 dequenching showed that vesicles from wild-type, Pep299-overexpressing, and Δ299 strains fused with comparable efficiency, indicating that differences in persistence arise from cargo composition rather than altered delivery efficiency. Together, these findings reveal that CSP QS coordinates biogenesis and selective cargo remodeling in S. mutans and identify Pep299-containing vesicles as a quorum-regulated mechanism promoting antibiotic persistence.IMPORTANCEQuorum sensing enables bacterial populations to coordinate adaptive behaviors, yet its influence on membrane vesicle biology is not fully understood. This study shows that competence-stimulating peptide (CSP) signaling in Streptococcus mutans not only increases vesicle production but also remodels vesicle protein cargo, including enrichment of the persistence-associated peptide Pep299. CSP-induced vesicles enhance the formation of persister cells through a cargo-dependent mechanism rather than through changes in vesicle-cell fusion. These findings uncover a previously unrecognized connection between quorum sensing and vesicle-mediated persistence and reveal a strategy through which S. mutans modulates community behavior and resilience within the oral biofilm environment. |
| Competing Interests: | The authors declare no conflict of interest. |
| Σχόλια: | Erratum in: J Bacteriol. 2026 Sep 18:e0046826. doi: 10.1128/jb.00468-26.. (PMID: 42757964) |
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| Grant Information: | RGPIN-2019-06454 Natural Sciences and Engineering Research Council of Canada |
| Contributed Indexing: | Keywords: Streptococcus mutans; antibiotic tolerance; membrane vesicles; peptide signaling; persister cells; quorum sensing |
| Substance Nomenclature: | 0 (Anti-Bacterial Agents) 0 (Bacterial Proteins) 0 (Membrane Proteins) 0 (competence factor, Streptococcus) |
| Entry Date(s): | Date Created: 20260714 Date Completed: 20260820 Latest Revision: 20260918 |
| Update Code: | 20260918 |
| PubMed Central ID: | PMC13492114 |
| DOI: | 10.1128/jb.00323-26 |
| PMID: | 42447300 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1098-5530 |
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| DOI: | 10.1128/jb.00323-26 |