Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon

Research output: Contribution to journalArticle


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.


  • Ioannis Gryllos
  • Renata Grifantini
  • Annalisa Colaprico
  • Shengmei Jiang
  • Emelia Deforce
  • Anders Hakansson
  • John L Telford
  • Guido Grandi
  • Michael R Wessels
External organisations
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area


  • Bacterial Proteins, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genes, Bacterial, Genetic Complementation Test, Magnesium, Mutation, Oligonucleotide Array Sequence Analysis, Plasmids, Protein Kinases, Regulon, Repressor Proteins, Reproducibility of Results, Signal Transduction, Streptococcus pyogenes
Original languageEnglish
Pages (from-to)671-683
Number of pages13
JournalMolecular Microbiology
Issue number3
Publication statusPublished - 2007 Aug
Publication categoryResearch
Externally publishedYes