{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:29:05Z","timestamp":1785432545269,"version":"3.56.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T90DE021990"],"award-info":[{"award-number":["T90DE021990"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                      strains expressing the collagen-binding protein Cnm are strongly associated with severe and recurrent dental caries, yet the mechanistic basis for their clinical enrichment alongside\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      remains unclear. Here, we investigated whether Cnm contributes to early cross-kingdom interactions that promote dual-species biofilm development. Using purified proteins, we found that\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      binds robustly to Cnm at levels comparable to those of glucosyltransferase B (GtfB) and higher than those of other\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      adhesins tested. Preincubation of collagen with Cnm inhibited fungal binding, indicating that Cnm cannot simultaneously engage collagen and\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      , and suggesting competition for the same or adjacent binding regions. Cnm expression significantly enhanced coaggregation with\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      in both collagen-free and collagen-rich environments. In early attachment assays, Cnm increased\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      adherence to collagen-coated surfaces and promoted\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      recruitment on uncoated surfaces, consistent with ligand-dependent binding specificity. Pre-coaggregation in saliva further enhanced the ability of Cnm\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      to attach to\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      . At 24 h, Cnm expression increased biomass and\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      CFUs exclusively on collagen-coated surfaces, regardless of sucrose availability. Together, these findings identify Cnm as a dual-binding adhesin that associates with either collagen or\n                      <jats:italic toggle=\"yes\">C. albicans,<\/jats:italic>\n                      depending on environmental context, thereby accelerating coaggregation, early colonization, and biofilm maturation. This mechanism provides a biological explanation for the co-enrichment of Cbp\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      seen in dental caries and highlights Cnm as a key mediator of cross-kingdom synergy in early biofilm formation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Dental caries is a multifactorial and polymicrobial disease in which the consumption of fermentable carbohydrates favors acidogenic and aciduric microorganisms at the expense of beneficial commensal bacteria, creating a dysbiotic environment.\n                        <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        establish a synergistic relationship that exacerbates dysbiosis, thereby promoting caries development and progression. The current paradigm of this cross-kingdom synergism centers on increased extracellular polysaccharide production and enhanced biofilm biomass in the presence of sucrose. Here, we show that the collagen-binding protein Cnm, produced by approximately 20% of\n                        <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                        isolates, promotes interspecies co-aggregation with\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        , facilitating interspecies attachment and early biofilm formation. Our findings expand the current paradigm by demonstrating that Cnm recruits\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        to the developing biofilm. This interaction may play a crucial role in the stability and virulence of early biofilm communities, particularly under low-sucrose conditions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01046-26","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:10:53Z","timestamp":1782825053000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <i>Streptococcus mutans<\/i>\n                    collagen-binding protein Cnm enhances early biofilm formation with\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-2946","authenticated-orcid":false,"given":"Callahan","family":"Katrak","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Oral Biology, University of Florida College of Dentistry","place":["Gainesville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Bautista","sequence":"additional","affiliation":[{"name":"Vaxcyte Inc.","place":["San Carlos, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Pepe","sequence":"additional","affiliation":[{"name":"Vaxcyte Inc.","place":["San Carlos, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Fairman","sequence":"additional","affiliation":[{"name":"Vaxcyte Inc.","place":["San Carlos, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-7348","authenticated-orcid":true,"given":"Jacqueline","family":"Abranches","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Oral Biology, University of Florida College of Dentistry","place":["Gainesville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Trends in oral health status: United States, 1988-1994 and 1999-2004","author":"UDoHaHS UD","year":"2007","unstructured":"UDoHaHS UD. 2007. 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