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Repression of virulence genes by phosphorylation‐dependent oligomerization ofCsrR at target promoters in S. pyogenes
Author(s) -
Miller Alita A.,
Engleberg N. Cary,
DiRita Victor J.
Publication year - 2001
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2001.02441.x
Subject(s) - promoter , psychological repression , biology , virulence , dna footprinting , streptococcus pyogenes , transcription factor , gene , phosphorylation , microbiology and biotechnology , dna binding protein , signal transduction , regulation of gene expression , genetics , gene expression , staphylococcus aureus , bacteria
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.