{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:24:38Z","timestamp":1791995078461,"version":"4.4.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,3,14]]},"abstract":"<jats:p>\n                    <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                    can be efficiently internalized\n by a variety of human epithelial cells. \u03b2-lactam antibiotics,\n commonly used to treat\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    infections, do not\n readily permeate mammalian cells. There is growing evidence that the\n ability of streptococci to enter host cells contributes to the frequent\n failure of antibiotics to eradicate the organism from infected\n individuals. Recent studies have suggested that host cell entry\n requires the formation of a complex of a bacterial fibronectin (Fn)\n binding protein (e.g., M1 protein or protein F1\/SfbI), human Fn, and\n the epithelial cell Fn receptor, integrin \u03b15\u03b21. We report here that\n a low molecular weight, nonpeptide antagonist of integrin \u03b15\u03b21,\n SJ755, can inhibit internalization of streptococci by primary human\n tonsillar epithelial cells and immortalized human epithelial (A549)\n cells, thus increasing the extent of bacterial killing by antibiotics.\n SJ755 blocked Fn binding by human tonsillar epithelial and A549 cells,\n suggesting that integrin \u03b15\u03b21 is the major Fn receptor expressed by\n both cell types. SJ755 did not affect Fn binding by purified M1 protein\n or M1\n                    <jats:sup>+<\/jats:sup>\n                    bacteria. Purified M1 protein failed to associate\n with integrin \u03b15\u03b21 unless the integrin had been prebound by Fn.\n Also, SJ755 blocked formation of \u03b15\u03b21-Fn-M1 complexes\n                    <jats:italic>in\n vitro<\/jats:italic>\n                    . These results support the previous proposal that Fn\n functions as a molecular bridge between M1 protein and integrin\n \u03b15\u03b21. Furthermore, these results suggest that integrin antagonists\n may enhance the efficacy of antibiotics in treatment of\n                    <jats:italic>S.\n pyogenes<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.050587897","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"2858-2863","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":86,"title":["A nonpetide integrin antagonist can inhibit epithelial cell ingestion of\n                    <i>Streptococcus pyogenes<\/i>\n                    by blocking formation of integrin \u03b15\u03b21-fibronectin-M1 protein complexes"],"prefix":"10.1073","volume":"97","author":[{"given":"David","family":"Cue","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarka O.","family":"Southern","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Southern","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadhar","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Lorelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M.","family":"Smallheer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaker A.","family":"Mousa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota, Minneapolis,\r MN 55455; and Dupont Pharmaceutical Experimental Station,\r Wilmington, DE 19880"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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