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Adhesion to streptococci is driven by interaction of the minor fimbrial antigen (Mfa1) with streptococcal antigen I\/II. We identified the region of antigen I\/II required for this interaction and developed small molecule mimetics that inhibited <jats:italic>P. gingivalis<\/jats:italic> adherence. However, the functional motifs of Mfa1 involved in the interaction with antigen I\/II remain uncharacterized. A series of N\u2010 and C\u2010terminal peptide fragments of Mfa1 were expressed and tested for inhibition of <jats:italic>P. gingivalis<\/jats:italic> adherence to <jats:italic>S. gordonii<\/jats:italic>. This approach identified residues 225\u2013400 of Mfa1 as essential for <jats:italic>P. gingivalis<\/jats:italic> adherence. Using the three\u2010dimensional structure of Mfa1, a putative binding cleft was identified using SiteMap and five small molecule mimetics could dock in this site. Site\u2010specific mutation of residues in the predicted cleft, including R240A, W275A, D321A and A357P inhibited the interaction of Mfa1 with streptococci, whereas mutation of residues not in the predicted cleft (V238A, I252F and \u0394K253) had no effect. Complementation of an Mfa1\u2010deficient <jats:italic>P. gingivalis<\/jats:italic> strain with wild\u2010type <jats:italic>mfa1<\/jats:italic> restored adherence to streptococci, whereas complementation with full\u2010length <jats:italic>mfa1<\/jats:italic> containing the R240A or A357P mutations did not restore adherence. The mutations did not affect polymerization of Mfa1, suggesting that the complemented strains produced intact minor fimbriae. These results identified specific residues and structural motifs required for the Mfa1\u2010antigen I\/II interaction and will facilitate the design of small molecule therapeutics to prevent <jats:italic>P. gingivalis<\/jats:italic> colonization of the oral cavity.<\/jats:p>","DOI":"10.1111\/omi.12280","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T04:55:02Z","timestamp":1580273702000},"page":"66-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of functional domains of the minor fimbrial antigen involved in the interaction of <i>Porphyromonas gingivalis<\/i> with oral streptococci"],"prefix":"10.1111","volume":"35","author":[{"given":"Mohammad","family":"Roky","sequence":"first","affiliation":[{"name":"Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville KY USA"},{"name":"Department of Microbiology 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