Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence.

摘要: Streptococcus agalactiae can cause urinary tract infection (UTI) including cystitis and asymptomatic bacteriuria (ABU). The early host-pathogen interactions that occur during S. UTI subsequent mechanisms of disease pathogenesis are poorly defined. Here, we define the between human bladder urothelial cells, monocyte-derived macrophages, mouse using uropathogenic (UPSA) 807 ABU-causing (ABSA) 834 strains. UPSA adhered, invaded killed cells more efficiently compared to ABSA via low-level caspase-3 activation, cytolysis, according lactate dehydrogenase release measures cell viability. Severe 807-induced cytotoxicity was mediated entirely by bacterial β-hemolysin/cytolysin (β-H/C) because an β-H/C-deficient isogenic mutant, 807ΔcylE, not cytotoxic in vitro; mutant also significantly attenuated for colonization vivo. Analysis infection-induced cytokines, IL-8, IL-1β, IL-6 TNF-α vitro vivo revealed cytokine chemokine responses were dependent on expression β-H/C elicited severe neutrophilia. Thus, virulence encompasses adhesion to, invasion killing pro-inflammatory cytokine/chemokine elicit neutrophil infiltration, β-H/C-mediated subversion innate immune-mediated clearance from bladder.