Repression of virulence genes by phosphorylation-dependent oligomerization of CsrR at target promoters in S. pyogenes.
csrRS encodes a two-component regulatory system that represses the transcription of a number of virulence factors in Streptococcus pyogenes, including the hyaluronic acid capsule and pyrogenic exotoxin B. CsrRS-regulated virulence factors have diverse functions during pathogenesis and are differentially expressed throughout growth. This suggests that multiple signals induce CsrRS-mediated gene regulation, or that regulated genes respond differently to CsrR, or both. As a first step in dissecting the csrRS signal transduction pathway, we determined the mechanism by which CsrR mediates the repression of its target promoters. We found that phosphorylated CsrR binds directly to all but one of the promoters of its regulated genes, with different affinities. Phosphorylation of CsrR enhances both oligomerization and DNA binding. We defined the binding site of CsrR at each of the regulated promoters using DNase I and hydroxyl radical footprinting. Based on these results, we propose a model for differential regulation by CsrRS.
Miller
A A
AA
Department of Microbiology and Immunology, Unit for Laboratory Animal Medicine, 5641 Medical Science II, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Engleberg
N C
NC
DiRita
V J
VJ
D001426:Bacterial Proteins; D001483:Base Sequence; D001665:Binding Sites; D004269:DNA, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D004269:DNA, Bacterial; D012097:Repressor Proteins; D011494:Protein Kinases; C432144:CsrS protein, bacteria