CsrRS and Environmental pH Regulate Group B Streptococcus Adherence to Human Epithelial Cells and Extracellular Matrix

Abstract

Streptococcus agalactiae (group B Streptococcus or GBS) is a common colonizer of the gastrointestinal and genital tracts and an important cause of invasive infections in newborn infants and in adults with predisposing chronic conditions or advanced age. Attachment to epithelial surfaces at mucosal sites is a critical step in the successful colonization of a human host, and regulation of this process is likely to play an important role in both commensalism and dissemination to cause invasive disease. We found that inactivation of the CsrRS (or CovRS) two-component system increased GBS adherence to epithelial cells derived from human vaginal, cervical, and respiratory epithelium, as well as increasing adherence to extracellular matrix proteins and increasing biofilm formation on polystyrene. Neutral (as opposed to acidic) pH enhanced GBS binding to vaginal epithelial cells and to fibrinogen and fibronectin, effects that were partially dependent on CsrRS. The regulatory effects of CsrRS and environmental pH on bacterial adherence correlated with their effects on the expression of multiple surface adhesins, as assessed by quantitative reverse transcription-PCR. We conclude that GBS adherence to epithelial and abiotic surfaces is regulated by the CsrRS twocomponent system and by environmental pH through their regulatory effects on the expression of bacterial surface adhesins. Dynamic regulation of GBS adherence enhances the organism's adaptability to survival in multiple niches in the human host.

BsaB, a Novel Adherence Factor of Group B Streptococcus

“…Biofilm assays were performed in 96-well polystyrene flat-bottom microtiter plates (Costar) as described previously (8,29,30). Each assay was performed in triplicate and repeated at least three times.…”

“…Plates coated with fibronectin or laminin were purchased from BD Biosciences. Adherence assays were performed as described previously (8). Assays were repeated at least three times in triplicate.…”

“…Several surface proteins have been characterized as adhesins that are involved in bacterial attachment to host cells and/or the extracellular matrix (ECM) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Members of one family of surface proteins contain the LPXTG anchor motif at the C terminus followed by a hydrophobic domain and a positively charged tail (17).…”

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

“…Mutants in the covRS locus, regardless of whether they are constructed in vitro or whether they occur spontaneously in animal models during experimental infections, render bacteria more virulent and highly invasive (Engleberg et al, 2001;Garcia et al, 2010;Heath et al, 1999). In S. agalactiae, the inactivation of covRS increases the expression of surface adhesins, and thus adhesion of the bacteria to human vaginal, cervical and respiratory epithelial cells, as well as to constituents of the extracellular matrix (Park et al, 2012).…”

In silico prediction of conserved vaccine targets in Streptococcus agalactiae strains isolated from fish, cattle, and human samples

“…In humans, it is frequently associated with neonatal sepsis and meningitis, but can also affect immunocompromised adults, besides also being a common colonizer of the gastrointestinal and genitourinary tracts (Park et al, 2012). In dairy cattle, GBS is an important pathogen of clinical and subclinical mastitis, affecting milk quality and production (Richards et al, 2011).…”