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dc.contributor.authorLeclercq, Sophie Y
dc.contributor.authorSullivan, Matthew J
dc.contributor.authorIpe, Deepak S
dc.contributor.authorSmith, Joshua P
dc.contributor.authorCripps, Allan W
dc.contributor.authorUlett, Glen C
dc.date.accessioned2018-01-18T04:33:48Z
dc.date.available2018-01-18T04:33:48Z
dc.date.issued2016
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/srep29000
dc.identifier.urihttp://hdl.handle.net/10072/99641
dc.description.abstractStreptococcus agalactiae can cause urinary tract infection (UTI) including cystitis and asymptomatic bacteriuria (ABU). The early host-pathogen interactions that occur during S. agalactiae 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 S. agalactiae (UPSA) 807 and ABU-causing S. agalactiae (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 β-hemolysin/cytolysin (β-H/C) because an β-H/C-deficient UPSA 807 isogenic mutant, UPSA 807ΔcylE, was not cytotoxic in vitro; the mutant was also significantly attenuated for colonization in the bladder in vivo. Analysis of infection-induced cytokines, including IL-8, IL-1β, IL-6 and TNF-α in vitro and in vivo revealed that cytokine and chemokine responses were dependent on expression of β-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 β-H/C-mediated subversion of innate immune-mediated bacterial clearance from the bladder.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Macmillan
dc.relation.ispartofpagefrom29000-1
dc.relation.ispartofpageto29000-14
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume6
dc.subject.fieldofresearchBacteriology
dc.subject.fieldofresearchcode060501
dc.titlePathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s). 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
gro.hasfulltextFull Text
gro.griffith.authorCripps, Allan W.
gro.griffith.authorUlett, Glen C.
gro.griffith.authorIpe, Deepak S.
gro.griffith.authorSmith, Josh P.
gro.griffith.authorSullivan, Matthew J.
gro.griffith.authorLeclercq, Sophie Y.


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