Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis.
Group B Streptococcus (GBS) (or Streptococcus agalactiae)is an important cause of invasive infection in newborn infants, in women around the time of childbirth, and in older individuals with underlying chronic illnesses (28). Although GBS has the capacity to produce life-threatening infection in susceptible hosts, more often it behaves as a harmless commensal organism. Surveys of asymptomatic volunteers have demonstrated that GBS colonizes the vagina and/or rectum of one-third to one-half of healthy women (12). Because GBS encounters a variety of environmental conditions in the varied niches it occupies, the organism's survival in the human host may be enhanced by its ability to perceive changes in the external milieu and to adapt by altering expression of specific genes. This dynamic adaptation of GBS to the human host is likely to involve one or more regulatory systems that control expression of bacterial factors important in adhesion, nutrient acquisition, resistance to host immune effectors, and under certain circumstances, invasion of host tissues.One mechanism for adaptation to changing environments is through two-component regulatory systems, a family of proteins that are widely distributed among many bacterial genera (20,32). Two-component systems allow sensing of specific environmental signals through a sensor histidine kinase that is usually associated with the cell membrane. In the basic mode...