{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:46:19Z","timestamp":1792424779368,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>This succinct article addresses the multifaceted interactions between the fungal organism <jats:italic>Candida albicans<\/jats:italic> and the Gram-positive bacterium <jats:italic>Streptococcus mutans<\/jats:italic> in the development of oral biofilms and pathobiology of oral diseases. <jats:italic>S. mutans<\/jats:italic> is considered to be a major pathogen in the development of dental caries. It is often found to interact with <jats:italic>C. albicans<\/jats:italic> in oral infection settings. The interaction of these organisms is often mediated via the binding of Glucosyltransferase (GtfB) enzyme secreted by <jats:italic>S. mutans<\/jats:italic> to <jats:italic>C. albicans<\/jats:italic> surface proteins Als1 and Hwp1. During these interactions, both <jats:italic>C. albicans<\/jats:italic> and <jats:italic>S. mutans<\/jats:italic> exhibit increased gene regulatory activity, leading to the modulation of virulence attributes and adaptation to environmental changes. This results in the strong attachment of the species to tooth surfaces and increased resistance of the mixed species biofilms to external factors. Mechanistically, intercellular communication between these species in mixed biofilms through quorum sensing and production of exoenzymes such as glucosyltransferases account for the synergy and modulation of their virulence attributes. Specifically, these mixed-species biofilms exhibit increased acid production and enhanced resistance to antimicrobial agents. Understanding these complex interkingdom pattern of interactions is essential to develop efficient therapeutic approaches against biofilm-associated oral infections. The review also highlights probiotic strategies to interfere with these interkingdom interactions to combat oral diseases like early childhood caries (ECC).<\/jats:p>","DOI":"10.3389\/fcimb.2025.1625103","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:32:53Z","timestamp":1751002373000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Multifaceted roles of Candida albicans and Streptococcus mutans in contributing to polybiofilm infections in early childhood caries"],"prefix":"10.3389","volume":"15","author":[{"given":"Anto Benignus","family":"Francis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra Prasad","family":"Settem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moghanram","family":"Jeyamoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata Harshith","family":"Nuthangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashu","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish Kumar","family":"Rajasekharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.12688\/f1000research.16275.2","article-title":"Relationship between Candida albicans and Streptococcus mutans in early childhood caries, evaluated by quantitative PCR","volume":"7","author":"Bachtiar","year":"2018","journal-title":"F1000Research"},{"key":"B2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1159\/000324598","article-title":"Biology of streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms","volume":"45","author":"Bowen","year":"2011","journal-title":"Caries Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/j.1365-2958.2010.07212.x","article-title":"The changing faces of Streptococcus antigen I\/II polypeptide family adhesins","volume":"77","author":"Brady","year":"2010","journal-title":"Mol. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.748656","article-title":"Oral mycobiome differences in various spatial niches with and without severe early childhood caries","volume":"9","author":"Cui","year":"2021","journal-title":"Front. Pediatr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1128\/IAI.05896-11","article-title":"Synergistic interaction between candida albicans and commensal oral streptococci in a novel in vitro mucosal model","volume":"80","author":"Diaz","year":"2012","journal-title":"Infect. Immun."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104876","article-title":"Candida and dental caries in children, adolescents and adults: A systematic review and meta-analysis","volume":"119","author":"Eidt","year":"2020","journal-title":"Arch. Oral. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e00339","DOI":"10.1128\/IAI.00339-19","article-title":"Multi-omics Analyses Reveal Synergistic Carbohydrate Metabolism in Streptococcus mutans-Candida albicans Mixed-Species Biofilms","volume":"87","author":"Ellepola","year":"2019","journal-title":"Infect. Immun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1128\/IAI.00087-14","article-title":"Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo","volume":"82","author":"Falsetta","year":"2014","journal-title":"Infect. Immun."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1128668","article-title":"Inhibitory effects of Stevioside on Streptococcus mutans and Candida albicans dual-species biofilm","volume":"14","author":"Guo","year":"2023","journal-title":"Front. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14124","article-title":"N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson\u2019s disease","volume":"23","author":"Guo","year":"2024","journal-title":"Aging Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006407","article-title":"Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo","volume":"13","author":"Hwang","year":"2017","journal-title":"PloS Pathog."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2024.2339161","article-title":"Unveiling the complexity of early childhood caries: Candida albicans and Streptococcus mutans cooperative strategies in carbohydrate metabolism and virulence","volume":"16","author":"Jin","year":"2024","journal-title":"J. Oral. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0315086","article-title":"Investigating the association between Candida albicans and early childhood dental caries: A comprehensive systematic review and meta-analysis","volume":"19","author":"Khachatryan","year":"2024","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.30574\/wjarr.2023.17.1.0066","article-title":"Review: Quorum sensing mechanism between Streptococcus mutans and Candida albicans in the pathogenesis of dental caries","volume":"17","author":"Kriswandini","year":"2023","journal-title":"World J. Adv. Res. Rev."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftac010","article-title":"Polymicrobial interaction in biofilm: mechanistic insights","volume":"80","author":"Kulshrestha","year":"2022","journal-title":"Pathog. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"7.1.03","DOI":"10.1128\/microbiolspec.GPP3-0051-2018","article-title":"The biology of streptococcus mutans","volume":"7","author":"Lemos","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1106231","article-title":"Current and prospective therapeutic strategies: tackling Candida albicans and Streptococcus mutans cross-kingdom biofilm","volume":"13","author":"Li","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1151532","article-title":"Roles of Streptococcus mutans-Candida albicans interaction in early childhood caries: a literature review","volume":"13","author":"Lu","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.identj.2024.08.020","article-title":"Oral candida-biome and early childhood caries: A systematic review and meta-analysis","volume":"75","author":"Man","year":"2025","journal-title":"Int. Dent. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jdsr.2017.08.002","article-title":"Role of Streptococcus mutans surface proteins for biofilm formation","volume":"54","author":"Matsumoto-Nakano","year":"2018","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fdmed.2022.849274","article-title":"Candida albicans and early childhood caries","volume":"3","author":"Menon","year":"2022","journal-title":"Front. Dent. Med."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003616","article-title":"Streptococcus mutans, Candida albicans, and the Human Mouth: A Sticky Situation","volume":"9","author":"Metwalli","year":"2013","journal-title":"PloS Pathog."},{"key":"B23","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/nrmicro2313","article-title":"Medically important bacterial\u2013fungal interactions","volume":"8","author":"Peleg","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/jof10050328","article-title":"A systematic review of denture stomatitis: predisposing factors, clinical features, etiology, and global candida spp. Distribution","volume":"10","author":"Peri\u0107","year":"2024","journal-title":"J. Fungi"},{"key":"B25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12903-024-05355-7","article-title":"Cordycepin affects Streptococcus mutans biofilm and interferes with its metabolism","volume":"25","author":"Shao","year":"2025","journal-title":"BMC Oral. Health"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1574-6968.2009.01668.x","article-title":"Cross-kingdom interactions: Candida albicans and bacteria","volume":"299","author":"Shirtliff","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"B27","doi-asserted-by":"publisher","first-page":"911","DOI":"10.3290\/j.ohpd.a45411","article-title":"Association of streptococcus mutans, candida albicans and oral health practices with activity status of caries lesions among 5-year-old children with early childhood caries","volume":"18","author":"Sridhar","year":"2020","journal-title":"Oral. Health Prev. Dent."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1038\/ismej.2014.73","article-title":"Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans","volume":"8","author":"Sztajer","year":"2014","journal-title":"ISME J."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/biology10060496","article-title":"Friends or foes\u2014Microbial interactions in nature","volume":"10","author":"Weiland-Br\u00e4uer","year":"2021","journal-title":"Biology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1177\/0022034518790941","article-title":"Association between oral candida and bacteriome in children with severe ECC","volume":"97","author":"Xiao","year":"2018","journal-title":"J. Dent. Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1625103\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:32:54Z","timestamp":1751002374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1625103\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":30,"alternative-id":["10.3389\/fcimb.2025.1625103"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1625103","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]},"article-number":"1625103"}}