{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:14:44Z","timestamp":1776744884222,"version":"3.51.2"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,2,5]],"date-time":"2003-02-05T00:00:00Z","timestamp":1044403200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Multiple regulatory mechanisms for coping with stress co\u2010exist in low G+C Gram\u2010positive bacteria. Among these, the HrcA and CtsR repressors control distinct regulons in the model organism, <jats:italic>Bacillus subtilis<\/jats:italic>. We recently identified an orthologue of the CtsR regulator of stress response in the major pathogen, <jats:italic>Staphylococcus aureus<\/jats:italic>. Sequence analysis of the <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> genome revealed the presence of potential CtsR operator sites not only upstream from genes encoding subunits of the Clp ATP\u2010dependent protease, as in <jats:italic>B<\/jats:italic>. <jats:italic>subtilis<\/jats:italic>, but also, unexpectedly, within the promoter regions of the <jats:italic>dnaK<\/jats:italic> and <jats:italic>groESL<\/jats:italic> operons known to be specifically controlled by HrcA. The tandem arrangement of the CtsR and HrcA operators suggests a novel mode of dual heat shock regulation by these two repressors. The <jats:italic>S<\/jats:italic>. <jats:italic>aureus ctsR<\/jats:italic> and <jats:italic>hrcA<\/jats:italic> genes were cloned under the control of the P<jats:italic>xylA<\/jats:italic> xylose\u2010inducible promoter and used to demonstrate dual regulation of the <jats:italic>dnaK<\/jats:italic> and <jats:italic>groESL<\/jats:italic> operons by both CtsR and HrcA, using <jats:italic>B<\/jats:italic>. <jats:italic>subtilis<\/jats:italic> as a heterologous host. Direct binding by both repressors was shown <jats:italic>in vitro<\/jats:italic> by gel mobility shift and DNase I footprinting experiments using purified <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> CtsR and HrcA proteins. \u0394<jats:italic>ctsR<\/jats:italic>, \u0394<jats:italic>hrcA<\/jats:italic> and \u0394<jats:italic>ctsR<\/jats:italic>\u0394<jats:italic>hrcA<\/jats:italic> mutants of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> were constructed, indicating that the two repressors are not redundant but, instead, act together synergistically to maintain low basal levels of expression of the <jats:italic>dnaK<\/jats:italic> and <jats:italic>groESL<\/jats:italic> operons in the absence of stress. This novel regulatory mode appears to be specific to Staphylococci.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2003.03355.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:47:22Z","timestamp":1047469642000},"page":"1061-1073","source":"Crossref","is-referenced-by-count":131,"title":["Comparative genomics reveal novel heat shock regulatory mechanisms in <i>Staphylococcus aureus<\/i> and other Gram\u2010positive 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