Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

The role of Streptococcus agalactiae CovR in urinary tract infection  (#146)

Matthew J Sullivan 1 , Sophie Y Leclercq 1 2 , Glen Ulett 1
  1. School of Medical Science, Griffith University, Gold Coast, Queensland, Australia
  2. Research and Development Center, Ezequiel Dias Foundation (FUNED), Belo Horizonte, Brazil

Up to 50% of humans experience urinary tract infections (UTI) during their life. Group B Streptococcus (GBS; Streptococcus agalactiae) can colonize the urinary tract and cause UTI in healthy adults, elderly and immunocompromised individuals. The mechanisms and virulence factors that influence GBS UTI are not fully elucidated. The CovRS two-component system regulates hundreds of genes in GBS, comprising a response receiver (CovS) and the DNA binding protein (CovR). Regulatory targets of CovR include cytotoxins, adhesins and capsular polysaccharide. Prior studies associate mutation in covR with hyper-virulence, partly due to the overexpression of the GBS β-hemolysin/cytolysin (β-h/c).

We show that CovR enhances the ability of GBS to cause acute UTI. Mutation in covR perturbed GBS colonisation of the bladder and urine in a mouse UTI model, and reduced the levels of adherence towards and invasion of human bladder uroepithelial cells. Mutation in covR also caused increased b-h/c activity, death of uroepithelial cells and caspase-3 activation. We saw altered immune responses during our in vitro and in vivo experiments for a number of pro-inflammatory cytokines and chemokines, including IL-6, IL-17A, GM-CSF and KC/IL-8, in a covR-dependent manner. Examination of several known CovR-regulated virulence factors revealed the adhesin gene hvgA partly explains the complex role of CovR in promoting UTI.

Collectively, these data highlight CovR as a central regulator of GBS virulence that influences the pathogenesis of UTI. We conclude the mechanisms underlying CovR-dependent phenotypes in UTI are complex and multifactorial due to the pleiotropic nature of the CovRS system in GBS.