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However, there are studies indicating that<jats:italic>Y. pestis<\/jats:italic>invades and causes systemic infection from ingestive and aerogenic routes of infection. Accordingly, we developed a gentamicin protection assay and reexamined invasiveness of<jats:italic>Y. pestis<\/jats:italic>for HeLa cells. By optimizing this assay, we discovered that<jats:italic>Y. pestis<\/jats:italic>is highly invasive. Several factors, including the presence of fetal bovine serum, the configuration of the tissue culture plate, the temperature at which the bacteria are grown, and the presence of the plasminogen activator protease Pla-encoding plasmid pPCP1, were found to influence invasiveness strongly. Suboptimal combinations of these factors may have contributed to negative findings by previous studies attempting to demonstrate invasion by<jats:italic>Y. pestis<\/jats:italic>. Invasion of HeLa cells was strongly inhibited by cytochalasin D and modestly inhibited by colchicine, indicating strong and modest respective requirements for microfilaments and microtubules. We found no significant effect of the iron status of yersiniae or of the pigmentation locus on invasion and likewise no significant effect of the Yops regulon. However, an unidentified thermally induced property (possibly the<jats:italic>Y. pestis<\/jats:italic>-specific capsular protein Caf1) did inhibit invasiveness significantly, and the plasmid pPCP1, unique to<jats:italic>Y. pestis<\/jats:italic>, was essential for highly efficient invasion. pPCP1 encodes an invasion-promoting factor and not just an adhesin, because<jats:italic>Y. pestis<\/jats:italic>lacking this plasmid still adhered to HeLa cells. These studies have enlarged our picture of<jats:italic>Y. pestis<\/jats:italic>biology and revealed the importance of properties that are unique to<jats:italic>Y. pestis<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.68.8.4523-4530.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:01:19Z","timestamp":1027764079000},"page":"4523-4530","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["Invasion of Epithelial Cells by<i>Yersinia pestis<\/i>: Evidence for a<i>Y. pestis<\/i>-Specific Invasin"],"prefix":"10.1128","volume":"68","author":[{"given":"Clarissa","family":"Cowan","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Jones","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin H.","family":"Kaya","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Perry","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan C.","family":"Straley","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02546.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.5.2567-2574.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1922-1928.1999"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(79)68018-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4851-4861.1999"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.36.3.1160-1167.1982"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/am.26.6.1016-1018.1973"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4049\/jimmunol.83.4.348","article-title":"The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of flea-borne plague","volume":"84","author":"Cavanaugh D. 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