title: Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon.
abstract: CsrRS (or CovRS) is a two-component system implicated in the control of multiple virulence determinants in the important human pathogen, group A Streptococcus (GAS). Earlier studies suggested that extracellular Mg(2+) signalled through the presumed sensor histidine kinase, CsrS. We now confirm those findings, as complementation of a csrS mutant restored Mg(2+)-dependent gene regulation. Moreover, we present strong evidence that Mg(2+) signals through CsrS to regulate an extensive and previously undefined repertoire of GAS genes. The effect of Mg(2+) on regulation of global gene expression was evaluated using genomic microarrays in an M-type 3 strain of GAS and in an isogenic csrS mutant. Unexpectedly, of the 72 genes identified in the Mg(2+)-stimulated CsrRS regulon, 42 were absent from the CsrR regulon (the latter being defined by comparison of wild-type and CsrR mutant transcriptomes at low Mg(2+)). We observed CsrS-dependent regulation of 72 of the 73 genes whose expression changed in response to elevated extracellular Mg(2+) in wild-type bacteria, a result that identifies CsrS as the principal, if not exclusive, sensor for extracellular Mg(2+) in GAS. To our knowledge, this study is the first to characterize global gene regulation by a GAS two-component system in response to a specific environmental stimulus.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gryllos
authors.forename: Renata
authors.initials: R
authors.lastname: Grifantini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Colaprico
authors.forename: Shengmei
authors.initials: S
authors.lastname: Jiang
authors.forename: Emelia
authors.initials: E
authors.lastname: Deforce
authors.forename: Anders
authors.initials: A
authors.lastname: Hakansson
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wessels
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D008274:Magnesium / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics*; D018085:Regulon / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D012097:Repressor Proteins; D011494:Protein Kinases; C432144:CsrS protein, bacteria; D008274:Magnesium