期刊
JOURNAL OF INFECTIOUS DISEASES
卷 215, 期 3, 页码 475-483出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw589
关键词
Urinary tract infection; Streptococcus agalactiae; covR; bladder; uroepithelium; virulence
资金
- NHMRC [APP1005315, APP1084889, APP1052464]
- Griffith Health Institute
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-Brazil
- Australian Research Council (Future Fellowship) [FT110101048]
Background. 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 beta-hemolysin/cytolysin (beta-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 beta-h/c and HvgA, but not capsule. Subsequent mutational analyses revealed that HvgA and capsule, but not the beta-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.
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