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

The two-component system response regulator LytR influences Group B Streptococcal colonization and disease (#27)

Liwen Deng 1 2 , Rong Mu 1 , Thomas Weston 1 , Roxanne Liles 3 , Kelly S Doran 1 2
  1. Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, CALIFORNIA, United States
  2. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, COLORADO, United States
  3. Louisiana State University , Alexandria, LOUISIANA, United States

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immune-compromised individuals, GBS may transition to an invasive pathogen and, despite currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains the leading cause of neonatal sepsis and meningitis. To adapt to various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCS). Several TCS have been shown to affect GBS virulence and we hypothesize that the previously uncharacterized LytSR TCS in GBS may also play a role pathogenesis. We have found that infection with the ΔlytR mutant GBS strain lacking the LytR transcriptional regulator causes increased secretion of inflammatory cytokines from human endothelial and epithelial cells. Additionally, the ΔlytR mutant is hypervirulent in our murine hematogenous meningitis model. Interestingly, while wild type GBS can colonize and persist in the mouse vaginal tract, the ΔlytR mutant is rapidly cleared. Further characterizing LytR signaling in GBS infection can provide insight into how the bacteria regulates its interaction with the host immune system and the effects of the host inflammatory response on disease progression. Ongoing RNA-sequencing studies are underway to identify downstream gene targets of the LytR regulator in order to better understand the changes in gene expression that occur during the transition between colonization and disease states. Ultimately, uncovering how LytR signaling affects bacterial persistence and virulence may inform the development of more effective therapies to prevent GBS infections.