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

Leclercq, Sophie Y., Sullivan, Matthew J., Ipe, Deepak S., Smith, Joshua P., Cripps, Allan W. and Ulett, Glen C. (2016) Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence. Scientific Reports, 6. ISSN 2045-2322

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Abstract

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 807 "cylE, 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.

Item Type: Article
Additional Information: Funding Information: This work was supported by National Health and Medical Research Council (NHMRC) Project Grants (APP1005315, APP1084889) and funding from the Griffith Health Institute, and the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)-Brazil (248427/2013-0 to SYL).
Uncontrolled Keywords: general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000
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Depositing User: LivePure Connector
Date Deposited: 15 Aug 2022 09:30
Last Modified: 26 Sep 2022 05:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/87232
DOI: 10.1038/srep29000

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