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dc.contributor.authorSullivan, Matthew J
dc.contributor.authorLeclercq, Sophie Y
dc.contributor.authorIpe, S
dc.contributor.authorCarey, Alison J
dc.contributor.authorSmith, Joshua P
dc.contributor.authorVoller, Nathan
dc.contributor.authorCripps, Allan W
dc.contributor.authorUlett, Glen C
dc.date.accessioned2017-06-18T23:16:14Z
dc.date.available2017-06-18T23:16:14Z
dc.date.issued2017
dc.identifier.issn0022-1899
dc.identifier.doi10.1093/infdis/jiw589
dc.identifier.urihttp://hdl.handle.net/10072/340075
dc.description.abstractBackground. Streptococcus agalactiae can cause urinary tract infection (UTI). The role of the S. agalactiae global virulence regulator, CovR, in UTI pathogenesis is unknown. Methods. We used murine and human bladder uroepithelial cell models of UTI and S. agalactiae mutants in covR and related factors, including β-hemolysin/cytolysin (β-h/c), surface-anchored adhesin HvgA, and capsule to study the role of CovR in UTI. Results. We found that covR-deficient serotype III S. agalactiae 874391 was significantly attenuated for colonization in mice and adhesion to uroepithelial cells. Mice infected with covR-deficient S. agalactiae produced less proinflammatory cytokines than those infected with wild-type 874391. Acute cytotoxicity in uroepithelial cells triggered by covR-deficient but not wild-type 874391 was associated with significant caspase 3 activation. Mechanistically, covR mutation significantly altered the expression of several genes in S. agalactiae 874391 that encode key virulence factors, including β-h/c and HvgA, but not capsule. Subsequent mutational analyses revealed that HvgA and capsule, but not the β-h/c, exerted significant effects on colonization of the murine urinary tract in vivo. Conclusions. S. agalactiae CovR promotes bladder infection and inflammation, as well as adhesion to and viability of uroepithelial cells. The pathogenesis of S. agalactiae UTI is complex, multifactorial, and influenced by virulence effects of CovR, HvgA, and capsule.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherOxford University Press
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto9
dc.relation.ispartofjournalThe Journal of Infectious Diseases
dc.subject.fieldofresearchMedical Bacteriology
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode110801
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.titleEffect of the Streptococcus agalactiae Virulence Regulator CovR on the Pathogenesis of Urinary Tract Infection
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorCripps, Allan W.
gro.griffith.authorUlett, Glen C.
gro.griffith.authorIpe, Deepak S.
gro.griffith.authorCarey, Alison
gro.griffith.authorSmith, Josh P.
gro.griffith.authorSullivan, Matthew J.
gro.griffith.authorVoller, Nathan M.
gro.griffith.authorLeclercq, Sophie Y.


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