Group B Streptococcus CovR regulation modulates host immune signalling pathways to promote vaginal colonization.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a frequent commensal organism of the vaginal tract of healthy women. However, GBS can transition to a pathogen in susceptible hosts, but host and microbial factors that contribute to this conversion are not well understood. GBS CovR/S (CsrR/S) is a two component regulatory system that regulates key virulence elements including adherence and toxin production. We performed global transcription profiling of human vaginal epithelial cells exposed to WT, CovR deficient, and toxin deficient strains, and observed that insufficient regulation by CovR and subsequent increased toxin production results in a drastic increase in host inflammatory responses, particularly in cytokine signalling pathways promoted by IL-8 and CXCL2. Additionally, we observed that CovR regulation impacts epithelial cell attachment and intracellular invasion. In our mouse model of GBS vaginal colonization, we further demonstrated that CovR regulation promotes vaginal persistence, as infection with a CovR deficient strainresulted in a heightened host immune response as measured by cytokine production and neutrophil activation. Using CXCr2 KO mice, we determined that this immune alteration occurs, at least in part, via signalling through the CXCL2 receptor. Taken together, we conclude that CovR is an important regulator of GBS vaginal colonization and loss of this regulatory function may contribute to the inflammatory havoc seen during the course of infection.

Patras KA ，Wang NY ，Fletcher EM ，Cavaco CK ，Jimenez A ，Garg M ，Fierer J ，Sheen TR ，Rajagopal L ，Doran KS ... -  《-》

Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration.

Lembo A ，Gurney MA ，Burnside K ，Banerjee A ，de los Reyes M ，Connelly JE ，Lin WJ ，Jewell KA ，Vo A ，Renken CW ，Doran KS ，Rajagopal L ... -  《-》

CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence.

Lamy MC ，Zouine M ，Fert J ，Vergassola M ，Couve E ，Pellegrini E ，Glaser P ，Kunst F ，Msadek T ，Trieu-Cuot P ，Poyart C ... -  《MOLECULAR MICROBIOLOGY》

Group B Streptococcus serotypes Ia and V induce differential vaginal immune responses that may contribute to long term colonization of the female reproductive tract.

Group B Streptococcus (GBS) is a common colonizer of the female genital tract at the time of pregnancy and has been associated with severe neonatal infections. Despite trials for GBS vaccines already being underway, the factors influencing vaginal GBS colonization and clearance are currently poorly understood. Within this study, we investigated the host immune responses to GBS infections in mice that affect GBS vaginal colonization and clearance. Cervicovaginal swabs were used to measure vaginal GBS persistence, and vaginal cytokine responses were measured using the BioPlex® system. Lymphocytes isolated from spleens were stimulated with UV-killed GBS to examine systemic cellular responses. Additional in vitro cellular experiments using human vaginal epithelial cells were also performed, examining the effect pregnancy level hormones had on GBS adhesion, invasion, and cytokine responses. We observed significant differences in the ability of GBS serotype V infections to persist, compared with GBS serotype Ia vaginal infections. Vaginal cytokine response examination identified temporal changes in cytokine production (IL10, IFNγ, IL6, IL1β, and TNFα) in relation to GBS serotype and clearance or colonization. Lymphocyte proliferation assays also revealed robust cellular immune responses to GBS vaginal infections irrespective of clearance or colonization. In vitro human cellular analyses also identified that vaginal epithelial cell line cytokine production was suppressed in the presence of hormones despite no alteration in adhesion/invasion. Here, we establish previously unknown, serotype specific, temporal immune responses which may be associated with vaginal GBS colonization or clearance in the female genital tract.

Sweeney EL ，Gardiner S ，Tickner J ，Trim L ，Beagley KW ，Carey AJ ... -  《-》

Serine-rich repeat proteins and pili promote Streptococcus agalactiae colonization of the vaginal tract.

Sheen TR ，Jimenez A ，Wang NY ，Banerjee A ，van Sorge NM ，Doran KS ... -  《-》