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The early host-pathogen interactions that occur during <jats:italic>S. agalactiae<\/jats:italic> UTI and subsequent mechanisms of disease pathogenesis are poorly defined. Here, we define the early interactions between human bladder urothelial cells, monocyte-derived macrophages, and mouse bladder using uropathogenic <jats:italic>S. agalactiae<\/jats:italic> (UPSA) 807 and ABU-causing <jats:italic>S. agalactiae<\/jats:italic> (ABSA) 834 strains. UPSA 807 adhered, invaded and killed bladder urothelial cells more efficiently compared to ABSA 834 via mechanisms including low-level caspase-3 activation, and cytolysis, according to lactate dehydrogenase release measures and cell viability. Severe UPSA 807-induced cytotoxicity was mediated entirely by the bacterial \u03b2-hemolysin\/cytolysin (\u03b2-H\/C) because an \u03b2-H\/C-deficient UPSA 807 isogenic mutant, UPSA 807\u0394<jats:italic>cylE<\/jats:italic>, was not cytotoxic <jats:italic>in vitro<\/jats:italic>; the mutant was also significantly attenuated for colonization in the bladder <jats:italic>in vivo<\/jats:italic>. Analysis of infection-induced cytokines, including IL-8, IL-1\u03b2, IL-6 and TNF-\u03b1 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> revealed that cytokine and chemokine responses were dependent on expression of \u03b2-H\/C that also elicited severe bladder neutrophilia. Thus, virulence of UPSA 807 encompasses adhesion to, invasion of and killing of bladder cells, pro-inflammatory cytokine\/chemokine responses that elicit neutrophil infiltration, and \u03b2-H\/C-mediated subversion of innate immune-mediated bacterial clearance from the bladder.<\/jats:p>","DOI":"10.1038\/srep29000","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T09:38:33Z","timestamp":1467884313000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and \u03b2-hemolysin\/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence"],"prefix":"10.1038","volume":"6","author":[{"given":"Sophie Y.","family":"Leclercq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak S.","family":"Ipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan W.","family":"Cripps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen C.","family":"Ulett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,7]]},"reference":[{"key":"BFsrep29000_CR1","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1007\/s15010-007-6180-2","volume":"35","author":"KB Laupland","year":"2007","unstructured":"Laupland, K. 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