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Bicarbonate‐mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium
Author(s) -
Yang Ji,
Hart Emily,
Tauschek Marija,
Price G. Dean,
Hartland Elizabeth L.,
Strugnell Richard A.,
RobinsBrowne Roy M.
Publication year - 2008
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 - 10.1111/j.1365-2958.2008.06171.x
Subject(s) - citrobacter rodentium , biology , virulence , citrobacter , operon , microbiology and biotechnology , genetics , gene , enterobacteriaceae , pathogen , escherichia coli
Summary Regulation of virulence gene expression plays a central role in the pathogenesis of enteric bacteria as they encounter diverse environmental conditions in the gastrointestinal tract of their hosts. In this study, we investigated environmental regulation of two putative virulence determinants adcA and kfc by RegA, an AraC/XylS‐like regulator, from Citrobacter rodentium , and identified bicarbonate as the environmental signal which induced transcription of adcA and kfc through RegA. Primer extension experiments showed that adcA and kfc were divergently transcribed from σ 70 promoters. In vivo and in vitro experiments demonstrated that bicarbonate facilitated and stabilized the binding of RegA to an operator located between the two promoters. The interaction of RegA with its DNA target resulted in the formation of a nucleosome‐like structure, which evidently displaced the histone‐like proteins, H‐NS and StpA, from the adcA and kfc promoter regions, leading to transcriptional derepression. In addition, our results indicated that RegA also behaved as a Class I activator by directly stimulating transcription initiation by RNA polymerase. This is the first report to describe the molecular mechanism by which an environmental chemical stimulates transcription of virulence‐associated genes of an enteric pathogen through an AraC/XlyS‐like activator.