{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:16:45Z","timestamp":1791044205807,"version":"4.1.0"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,10]]},"abstract":"<jats:p>\n                    <jats:italic>Actinobacillus actinomycetemcomitans<\/jats:italic>\n                    is a Gram-negative  coccobacillus that has been associated with localized aggressive periodontitis  and infections of the heart, brain, and urinary tract. Wild-type clinical  isolates have the remarkable ability to adhere tenaciously and nonspecifically  to solid surfaces such as glass, plastic, and hydroxyapatite. Adherence by\n                    <jats:italic>A. actinomycetemcomitans<\/jats:italic>\n                    is mediated by the tight-adherence  (\n                    <jats:italic>tad<\/jats:italic>\n                    ) gene locus, which consists of 14 genes  (\n                    <jats:italic>flp-1\u2013flp-2\u2013tadV\u2013rcpCAB\u2013tadZABCDEFG<\/jats:italic>\n                    ). All  but 2 of the genes have been shown to be required for the secretion and  assembly of long, bundled Flp1 fibrils. To test whether the\n                    <jats:italic>tad<\/jats:italic>\n                    locus  is required for colonization and disease, we developed a rat model for  periodontal disease. To mimic the natural route of infection,  Sprague\u2013Dawley rats were inoculated orally by adding bacteria directly  to their food for 8 days. After inoculation with wild-type or mutant strains  defective in adherence (\n                    <jats:italic>flp-1<\/jats:italic>\n                    and\n                    <jats:italic>tadA<\/jats:italic>\n                    ), the rats were  assessed for colonization of the oral cavity and pathogenesis. Wild-type\n                    <jats:italic>A. actinomycetemcomitans<\/jats:italic>\n                    was able to colonize and persist for at  least 12 weeks in the oral cavity, elicit a humoral immune response, and cause  significant bone loss in rats. In contrast, rats fed\n                    <jats:italic>flp-1<\/jats:italic>\n                    or\n                    <jats:italic>tadA<\/jats:italic>\n                    mutant strains showed no bone loss and their immune responses  were indistinguishable from those of the uninoculated controls. These results  demonstrate the critical importance of the\n                    <jats:italic>tad<\/jats:italic>\n                    locus in the  colonization and pathogenesis of\n                    <jats:italic>A. actinomycetemcomitans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.1237223100","type":"journal-article","created":{"date-parts":[[2003,6,10]],"date-time":"2003-06-10T13:06:36Z","timestamp":1055250396000},"page":"7295-7300","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":150,"title":["Tight-adherence genes of\n                    <i>Actinobacillus actinomycetemcomitans<\/i>\n                    are required for virulence in a rat model"],"prefix":"10.1073","volume":"100","author":[{"given":"Helen C.","family":"Schreiner","sequence":"first","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Sinatra","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Furgang","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Kachlany","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Planet","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda A.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Figurski","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Fine","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental  School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103;  and Department of Microbiology, College of  Physicians and Surgeons, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,5,19]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.61.2.136-169.1997"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(01)00067-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.1.46"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1985.tb01348.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1999.4.1.1"},{"key":"e_1_3_2_6_2","first-page":"14","volume":"51","year":"2002","unstructured":"Araujo, M. 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