title: Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity.
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.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Sheng-Mei
authors.initials: SM
authors.lastname: Jiang
authors.forename: Nadeeza
authors.initials: N
authors.lastname: Ishmael
authors.forename: Julie
authors.initials: J
authors.lastname: Dunning Hotopp
authors.forename: Manuela
authors.initials: M
authors.lastname: Puliti
authors.forename: Luciana
authors.initials: L
authors.lastname: Tissi
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kumar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cieslewicz
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wessels
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D018085:Regulon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins