Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity.

Division of Infectious Diseases, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
Journal of bacteriology (Impact Factor: 2.69). 04/2008; 190(6):1956-65. DOI: 10.1128/JB.01677-07
Source: PubMed

ABSTRACT CsrRS (or CovRS) is a two-component regulatory system that controls expression of multiple virulence factors in the important human pathogen group B Streptococcus (GBS). We now report global gene expression studies in GBS strains 2603V/R and 515 and their isogenic csrR and csrS mutants. Together with data reported previously for strain NEM316, the results reveal a conserved 39-gene CsrRS regulon. In vitro phosphorylation-dependent binding of recombinant CsrR to promoter regions of both positively and negatively regulated genes suggests that direct binding of CsrR can mediate activation as well as repression of target gene expression. Distinct patterns of gene regulation in csrR versus csrS mutants in strain 2603V/R compared to 515 were associated with different hierarchies of relative virulence of wild-type, csrR, and csrS mutants in murine models of systemic infection and septic arthritis. We conclude that CsrRS regulates a core group of genes including important virulence factors in diverse strains of GBS but also displays marked variability in the repertoire of regulated genes and in the relative effects of CsrS signaling on CsrR-mediated gene regulation. Such variation is likely to play an important role in strain-specific adaptation of GBS to particular host environments and pathogenic potential in susceptible hosts.

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Available from: Julie C Dunning Hotopp, Jul 15, 2015
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    • "The TCS CovRS (also known as CsrRS) is shared by several streptococcal species (including Group A Streptococcus or GAS) and is considered as the master regulator of virulence gene expression in GBS [8] [9]. Accordingly, the CovRS system regulates up to 7% of the GBS genes, most of which encode putative secreted or surface components, including several small molecule transport systems, cytolysins, and adhesins [7] [10]. "
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    ABSTRACT: The two-component regulatory system CovRS is the main regulator of virulence gene expression in Group B Streptococcus (GBS), the leading cause of invasive infections in neonates. In this study we analyzed by mass spectrometry the GBS extracellular protein complex (i.e. the exoproteome) of NEM316 wild-type (WT) strain and its isogenic covRS deletion mutant (ΔcovRS). A total of 53 proteins, 49 of which had classical secretion signals, were identified: 12 were released by both strains while 21 and 20 were released exclusively by WT and ΔcovRS strains, respectively. In addition to known surface proteins, we detected here unstudied cell-wall associated proteins and/or orthologs of putative virulence factors present in other pathogenic streptococci. While the functional role of these proteins remains to be elucidated, our data suggest that analysis of the exoproteome of bacterial pathogens under different gene expression conditions may be a powerful tool for the rapid identification of novel virulence factors and vaccine candidates. "SIGNIFICANCE": We believe this manuscript will be of interest to Journal of Proteomics readers since the paper describes the identification of several putative virulence factors and vaccine candidates of the group B streptococcus, an important pathogen, using a simple proteomics strategy involving LC-MS analysis of culture supernantants obtained from two strains with divergent gene expression patterns. This technique provided the most comprehensive inventory of extracellular proteins obtained from a single a streptococcal species thus far. The approach described has the added benefit of being easily applicable to a large number of different strains, making it ideal for the identification of conserved vaccine candidates.
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    • "Recently Rajagopal et al. (2006) linked phosphorylation of CovR by a Ser–Thr kinase to regulation of cytotoxin expression in S. agalactiae. A broad range of other studies of the role of the CovR(CsrR)-type regulators have been reported (Miller et al., 2001; Lamy et al., 2004; Orihuela et al., 2004; Gao et al., 2005; Jiang et al., 2008). "
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