{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:07:31Z","timestamp":1771556851467,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:00:00Z","timestamp":1610755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Periodontal disease (PD) is a progressive inflammatory condition characterized by degradation of the gingival epithelium, periodontal ligament, and alveolar bone ultimately resulting in tooth loss. Treponema denticola is a keystone periopathogen that contributes to immune dysregulation and direct tissue destruction. As periodontal disease develops, T. denticola must adapt to environmental, immunological and physiochemical changes in the subgingival crevice. Treponema denticola produces bis-(3\u2032-5\u2032)-cyclic dimeric guanosine monophosphate (c-di-GMP), an important regulatory nucleotide. While T. denticola encodes several putative diguanylate cyclases (DGCs), none have been studied and hence the biological role of c-di-GMP in oral treponemes remains largely unexplored. Here, we demonstrate that the T. denticola open reading frame, TDE0125, encodes a functional DGC designated as DgcA (Diguanylate cyclase A). The dgcA gene is universal among T. denticola isolates, highly conserved and is a stand-alone GGEEF protein with a GAF domain. Recombinant DgcA converts GTP to c-di-GMP using either manganese or magnesium under aerobic and anaerobic reaction conditions. Size exclusion chromatography revealed that DgcA exists as a homodimer and in larger oligomers. Site-directed mutagenesis of residues that define the putative inhibitory site of DgcA suggest that c-di-GMP production is allosterically regulated. This report is the first to characterize a DGC of an oral treponeme.<\/jats:p>","DOI":"10.1093\/femspd\/ftab004","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T09:26:58Z","timestamp":1610616418000},"source":"Crossref","is-referenced-by-count":9,"title":["The<i>Treponema denticola<\/i>DgcA protein (TDE0125) is a functional diguanylate cyclase"],"prefix":"10.1093","volume":"79","author":[{"given":"Dhara T","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, VCU Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, PO Box 980678, Richmond, VA 23298-0678, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathaniel S","family":"O'Bier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, VCU Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, PO Box 980678, Richmond, VA 23298-0678, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J A","family":"Schuler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, VCU Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, PO Box 980678, Richmond, VA 23298-0678, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-7306","authenticated-orcid":false,"given":"Richard T","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, VCU Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, PO Box 980678, Richmond, VA 23298-0678, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,16]]},"reference":[{"key":"2021032118144859300_bib1","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1128\/JB.00610-13","article-title":"Inactivation of cyclic di-gmp binding protein tde0214 affects the motility, biofilm formation, and virulence of treponema denticola","volume":"195","author":"Bian","year":"2013","journal-title":"J Bacteriol"},{"key":"2021032118144859300_bib2","doi-asserted-by":"crossref","first-page":"17084","DOI":"10.1073\/pnas.0406134101","article-title":"Structural basis of activity and allosteric control of diguanylate cyclase","volume":"101","author":"Chan","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032118144859300_bib3","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1042\/BCJ20180079","article-title":"The gdp-switched gaf domain of dcpa modulates the concerted synthesis\/hydrolysis of c-di-gmp in mycobacterium smegmatis","volume":"475","author":"Chen","year":"2018","journal-title":"Biochem J"},{"key":"2021032118144859300_bib4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1128\/JB.170.12.5789-5796.1988","article-title":"Selective release of the treponema pallidum outer membrane and associated polypeptides with triton x-114","volume":"170","author":"Cunningham","year":"1988","journal-title":"J Bacteriol"},{"key":"2021032118144859300_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmb.2009.08.030","article-title":"Determinants for the activation and autoinhibition of the diguanylate cyclase response regulator wspr","author":"De","year":"2009","journal-title":"J Mol Biol"},{"key":"2021032118144859300_bib6","doi-asserted-by":"crossref","first-page":"5002","DOI":"10.1128\/JB.00542-10","article-title":"The human oral microbiome","volume":"192","author":"Dewhirst","year":"2010","journal-title":"J Bacteriol"},{"key":"2021032118144859300_bib7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12203","article-title":"The periodontal pocket","volume":"76","author":"Donos","year":"2018","journal-title":"Periodontol 2000"},{"key":"2021032118144859300_bib8","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1365-2958.2010.07103.x","article-title":"Identification of residues within ligand-binding domain 1 (lbd1) of the borrelia burgdorferi ospc protein required for function in the mammalian environment","volume":"76","author":"Earnhart","year":"2010","journal-title":"Mol Microbiol"},{"key":"2021032118144859300_bib9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1600-0757.2005.00108.x","article-title":"Spirochetes at the forefront of periodontal infections","volume":"38","author":"Ellen","year":"2005","journal-title":"Periodontol 2000"},{"key":"2021032118144859300_bib10","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1099\/ijs.0.002287-0","article-title":"Treponema pedis sp. 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