{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:46Z","timestamp":1790676646306,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Shigella flexneri<\/jats:italic>is the causative agent of dysentery, and its pathogenesis is mediated by a type III secretion system (T3SS).<jats:italic>S. flexneri<\/jats:italic>secretes effector proteins into the eukaryotic cell via the T3SS, and these proteins usurp host cellular functions to the benefit of the bacteria. OspF and OspC1 are known to be secreted by<jats:italic>S. flexneri<\/jats:italic>, but their functions are unknown. We transformed<jats:italic>S. flexneri<\/jats:italic>with a plasmid that expresses a two-hemagglutinin tag (2HA) in frame with OspF or OspC1 and verified that these proteins are secreted in a T3SS-dependent manner. Immunofluorescence of HeLa cells infected with<jats:italic>S. flexneri<\/jats:italic>expressing OspF-2HA or OspC1-2HA revealed that both proteins localize in the nucleus and cytoplasm of host cells. To elucidate the function of these T3SS effectors, we constructed \u0394<jats:italic>ospF<\/jats:italic>and \u0394<jats:italic>ospC1<\/jats:italic>deletion mutants by allelic exchange. We found that \u0394<jats:italic>ospF<\/jats:italic>and \u0394<jats:italic>ospC1<\/jats:italic>mutants invade host cells and form plaques in confluent monolayers similar to wild-type<jats:italic>S. flexneri<\/jats:italic>. However, in the polymorphonuclear (PMN) cell migration assay, a decrease in neutrophil migration was observed for both mutants in comparison to the migration of wild-type bacteria. Moreover, infection of polarized T84 intestinal cells infected with \u0394<jats:italic>ospF<\/jats:italic>and \u0394<jats:italic>ospC1<\/jats:italic>mutants resulted in decreased phosphorylation of extracellular signal-regulated kinase 1\/2 in comparison to that of T84 cells infected with wild-type<jats:italic>S. flexneri<\/jats:italic>. To date, these are the first examples of T3SS effectors implicated in mitogen-activated protein kinase kinase\/extracellular signal-regulated kinase pathway activation. Ultimately, OspF and OspC1 are essential for PMN transepithelial migration, a phenotype associated with increased inflammation and bacterial access to the submucosa, which are fundamental aspects of<jats:italic>S. flexneri<\/jats:italic>pathogenesis.<\/jats:p>","DOI":"10.1128\/iai.00594-06","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T23:06:35Z","timestamp":1158793595000},"page":"5964-5976","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":71,"title":["OspF and OspC1 Are<i>Shigella flexneri<\/i>Type III Secretion System Effectors That Are Required for Postinvasion Aspects of Virulence"],"prefix":"10.1128","volume":"74","author":[{"given":"Daniel V.","family":"Zurawski","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Mitsuhata","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Mumy","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Maurelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.10.4005-4010.1997"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02179.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth804"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/323035"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.6.3608-3619.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.75.5.604-610.1958"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.14.4121-4130.1995"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.32.1.137-144.1981"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(83)80284-8"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.4052-4058.2003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04568.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/291238a0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03730.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.2.379-433.1998"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1046\/j.1365-2958.2003.03590.x","volume":"49","year":"2003","unstructured":"Jouihri, N., M. 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