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

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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
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	15 Aug 2022 09:30
Last Modified:	06 Feb 2025 10:47
URI:	https://ueaeprints.uea.ac.uk/id/eprint/87232
DOI:	10.1038/srep29000

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