{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:54:40Z","timestamp":1781848480839,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Capnocytophaga ochracea<\/jats:italic>\n                      , an early colonizer of oral biofilms associated with gingivitis, plays an incompletely understood role in periodontal pathogenesis. While sialidases are established virulence factors in late-colonizing \u2018red-complex\u2019 pathogens, their function in early colonizers, such as\n                      <jats:italic>C. ochracea<\/jats:italic>\n                      , remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To address this knowledge gap, we identified and characterized Co-NanH, the sole sialidase of\n                      <jats:italic>C. ochracea<\/jats:italic>\n                      . We performed phylogenetic and structural analyses to compare it with known sialidases. Enzymatic assays were conducted using recombinant Co-NanH to determine its pH optimum, substrate specificity, and kinetic parameters. Furthermore, we utilized sialidase inhibitors (such as DANA) and generated a\n                      <jats:italic>nanH<\/jats:italic>\n                      genetic deletion mutant (\n                      <jats:italic>\u0394nanH<\/jats:italic>\n                      ) to assess the enzyme\u2019s role in planktonic growth, biofilm formation, and interactions with human gingival epithelial cells (adhesion and internalization).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phylogenetic and structural analyses revealed that Co-NanH shares significant homology with a sialidase from\n                      <jats:italic>Tannerella forsythia<\/jats:italic>\n                      but possesses a distinct Sec\/SPI signal peptide and a monomeric structure. Recombinant Co-NanH exhibited optimal activity at pH 5.5 and cleaved both \u03b12,3- and \u03b12,6-linked sialic acids, with kinetic parameters comparable to those of red-complex pathogen sialidases. Inhibitors like DANA potently suppressed its activity and reduced\n                      <jats:italic>C. ochracea<\/jats:italic>\n                      biofilm formation. Crucially, genetic deletion of\n                      <jats:italic>nanH<\/jats:italic>\n                      abolished sialidase activity without affecting planktonic growth. The\n                      <jats:italic>\u0394nanH<\/jats:italic>\n                      mutant exhibited severely impaired biofilm formation, characterized by reduced biomass, thickness, and initial attachment. Furthermore, the mutant showed significantly reduced adhesion to and internalization by human gingival epithelial cells compared with wild-type and complemented strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings establish Co-NanH as a key mediator of\n                      <jats:italic>C. ochracea<\/jats:italic>\n                      in biofilm maturation and host cell interactions, revealing a functional parallel between early colonizers and classical periodontal pathogens. This work provides functional evidence that sialidase activity in an early colonizer contributes to oral dysbiosis by facilitating biofilm development and priming the host environment for disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1841812","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:47:05Z","timestamp":1781848025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Capnocytophaga ochracea sialidase drives its biofilm maturation and host cell interactions"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"He","sequence":"first","affiliation":[{"name":"Department of Endodontics, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"College of Stomatology, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"National Clinical Research Center for Oral Diseases, National Center for Stomatology","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Stomatology","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000788","article-title":"Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota","volume":"18","author":"Agarwal","year":"2020","journal-title":"PloS Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41579-023-00963-6","article-title":"The oral microbiome: Diversity, biogeography and human health","volume":"22","author":"Baker","year":"2024","journal-title":"Nat. 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