title: β-Hemolysin/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection.
abstract: Group B Streptococcus (GBS; Streptococcus agalactiae) is a major human pathogen that disproportionately affects neonates and women in the peripartum period and is an emerging cause of infection in older adults. The primary toxin of GBS, β-hemolysin/cytolysin (βH/C), has a well-defined role in the pathogenesis of invasive disease, but its role in urinary tract infection (UTI) is unknown. Using both in vitro and in vivo models, we analyzed the importance of βH/C in GBS uropathogenesis. There were no significant differences in bacterial density from the bladders or kidneys from mice infected with wild-type or isogenic βH/C-deficient GBS, and competitive indices from co-infection experiments were near 1. Thus, βH/C is dispensable for the establishment of GBS-UTI. However, βH/C-sufficient GBS induced a more robust proinflammatory cytokine response in cultured bladder epithelial cells and in the urinary tracts of infected mice. Given the near ubiquity of βH/C-expressing strains in epidemiologic studies and the importance of local inflammation in dictating outcomes and sequelae of UTI, we hypothesize that βH/C-driven inflammatory signaling may be important in the clinical course of GBS-UTI.
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York, United States of America.
authors.forename: Ritwij
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Tara M
authors.initials: TM
authors.lastname: Randis
authors.forename: Swati
authors.initials: S
authors.lastname: Antala
authors.forename: Alice
authors.initials: A
authors.lastname: Wang
authors.forename: Fábio E
authors.initials: FE
authors.lastname: Amaral
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism / Q000382:microbiology; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D013290:Streptococcal Infections / Q000378:metabolism / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000378:metabolism / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D006460:Hemolysin Proteins; D054353:Perforin; C071495:streptococcal group B hemolysin