9 research outputs found
Complete Genome Sequence of Serotype III Streptococcus agalactiae Sequence Type 17 Strain 874391
Here we report the complete genome sequence of Streptococcus agalactiae strain 874391. This serotype III isolate is a member of the hypervirulent sequence type 17 (ST-17) lineage that causes a disproportionate number of cases of invasive disease in humans and mammals. A brief historical context of the strain is discussed
Increased Age, but Not Parity Predisposes to Higher Bacteriuria Burdens Due to Streptococcus Urinary Tract Infection and Influences Bladder Cytokine Responses, Which Develop Independent of Tissue Bacterial Loads
Streptococcus agalactiae causes urinary tract infection (UTI) in pregnant adults, non-pregnant adults, immune-compromised individuals and the elderly. The pathogenesis of S. agalactiae UTI in distinct patient populations is poorly understood. In this study, we used murine models of UTI incorporating young mice, aged and dam mice to show that uropathogenic S. agalactiae causes bacteriuria at significantly higher levels in aged mice compared to young mice and this occurs coincident with equivalent levels of bladder tissue colonisation at 24 h post-infection (p.i.). In addition, aged mice exhibited significantly higher bacteriuria burdens at 48 h compared to young mice, confirming a divergent pattern of bacterial colonization in the urinary tract of aged and young mice. Multiparous mice, in contrast, exhibited significantly lower urinary titres of S. agalactiae compared to age-matched nulliparous mice suggesting that parity enhances the ability of the host to control S. agalactiae bacteriuria. Additionally, we show that both age and parity alter the expression levels of several key regulatory and pro-inflammatory cytokines, which are known to be important the immune response to UTI, including Interleukin (IL)-1β, IL-12(p40), and Monocyte Chemoattractant Protein-1 (MCP-1). Finally, we demonstrate that other cytokines, including IL-17 are induced significantly in the S. agalactiae-infected bladder regardless of age and parity status. Collectively, these findings show that the host environment plays an important role in influencing the severity of S. agalactiae UTI; infection dynamics, particularly in the context of bacteriuria, depend on age and parity, which also affect the nature of innate immune responses to infection
Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence
Streptococcus 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.Full Tex