{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:10:27Z","timestamp":1791832227754,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012887","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370947"],"award-info":[{"award-number":["82370947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"\n The ecological interplay between\n Streptococcus mutans<\/jats:italic>\n and\n Candida albicans<\/jats:italic>\n within dental plaque biofilms is an important factor driving pathogenesis of dental caries. This study aimed to investigate\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n regulation of\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n growth and virulence through extracellular membrane vesicles (EMVs) and modulation of ubiquitination, a key protein post-translational modification. We established a transwell co-culture model to enable \u201ccontact-independent\u201d interactions between\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n and\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n .\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n EMVs were found to directly associate with\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n cells and promote biofilm formation and growth. Quantitative ubiquitination profiling revealed\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n dramatically alters the ubiquitination landscape in\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n . We identified 10,661 ubiquitination sites across the\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n proteome and their enrichment in pathways related to translation, metabolism, and stress adaptation. Co-culture with\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n led to upregulation of ubiquitination on 398 proteins involved in sugar catabolism and generation of reducing power.\n S<\/jats:italic>\n .\n mutans<\/jats:italic>\n upregulated ubiquitination of superoxide dismutase-3 of\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n , inducing its degradation and heightened reactive oxygen species levels, and concomitantly stimulated\n C<\/jats:italic>\n .\n albicans<\/jats:italic>\n growth. Our findings elucidate EMVs and ubiquitination modulation as key mechanisms governing the\n S<\/jats:italic>\n .\n mutans-C<\/jats:italic>\n .\n albicans<\/jats:italic>\n interplay and provide new insights into the promotion of a cariogenic oral biofilm environment. This study significantly advances understanding of the complex molecular interactions underlying dental plaque dysbiosis and caries pathogenesis.\n <\/jats:p>","DOI":"10.1371\/journal.ppat.1012887","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T13:49:59Z","timestamp":1738590599000},"page":"e1012887","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Streptococcus mutans regulates ubiquitin modification of Candida albicans in the bacterial-fungal 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