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Effect of the Streptococcus agalactiae Virulence Regulator CovR on the Pathogenesis of Urinary Tract Infection
Journal article   Open access   Peer reviewed

Effect of the Streptococcus agalactiae Virulence Regulator CovR on the Pathogenesis of Urinary Tract Infection

Matthew J Sullivan, Sophie Y Leclercq, Deepak S Ipe, Alison J Carey, Joshua P Smith, Nathan Voller, Allan W Cripps and Glen C Ulett
The Journal of infectious diseases, v 215(3), pp 475-483
01 Feb 2017
DOI: https://doi.org/10.1093/infdis/jiw589
PMID: 28011914
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://academic.oup.com/jid/article-pdf/215/3/475/10878440/jiw589.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/infdis/jiw589View
Published, Version of Record (VoR) Open

Abstract

Adhesins, Bacterial - physiology Animals Bacterial Adhesion Bacterial Capsules - physiology Bacterial Proteins - physiology Cell Line Cytokines - metabolism Cytotoxicity, Immunologic Female Gene Expression Humans Mice Mice, Inbred C57BL Polymerase Chain Reaction Streptococcus agalactiae - pathogenicity Urinary Bladder - metabolism Urinary Tract Infections - microbiology Urothelium - microbiology Virulence Factors - physiology
Streptococcus agalactiae can cause urinary tract infection (UTI). The role of the S. agalactiae global virulence regulator, CovR, in UTI pathogenesis is unknown. 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. 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. 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.

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25 citations in Web of Science
27 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Infectious Diseases
Microbiology
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