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Here, we report the role of CodY in<jats:italic>Bacillus anthracis<\/jats:italic>, the etiologic agent of anthrax. Disruption of<jats:italic>codY<\/jats:italic>completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of CodY is required for full virulence of<jats:italic>B. anthracis<\/jats:italic>. Global transcriptome analysis of a<jats:italic>codY<\/jats:italic>mutant and the parental strain revealed extensive differences. These differences could reflect direct control for some genes, as suggested by the presence of CodY binding sequences in their promoter regions, or indirect effects via the CodY-dependent control of other regulatory proteins or metabolic rearrangements in the<jats:italic>codY<\/jats:italic>mutant strain. The differences included reduced expression of the anthrax toxin genes in the mutant strain, which was confirmed by<jats:italic>lacZ<\/jats:italic>reporter fusions and immunoblotting. The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain. However, in agreement with the microarray data, expression of<jats:italic>atxA<\/jats:italic>, as measured using an<jats:italic>atxA-lacZ<\/jats:italic>transcriptional fusion and by assaying<jats:italic>atxA<\/jats:italic>mRNA, was not significantly affected in the<jats:italic>codY<\/jats:italic>mutant. An<jats:italic>atxA-lacZ<\/jats:italic>translational fusion was also unaffected. Overexpression of<jats:italic>atxA<\/jats:italic>restored toxin component synthesis in the<jats:italic>codY<\/jats:italic>mutant strain. These results suggest that CodY controls toxin gene expression by regulating AtxA accumulation posttranslationally.<\/jats:p>","DOI":"10.1128\/iai.00716-09","type":"journal-article","created":{"date-parts":[[2009,8,4]],"date-time":"2009-08-04T16:07:37Z","timestamp":1249402057000},"page":"4437-4445","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["The Global Regulator CodY Regulates Toxin Gene Expression in<i>Bacillus anthracis<\/i>and Is Required for Full Virulence"],"prefix":"10.1128","volume":"77","author":[{"given":"Willem","family":"van Schaik","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unite\u0301 Toxines et Pathoge\u0301nie Bacte\u0301rienne, CNRS, URA 2172, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Cha\u0302teau","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 Toxines et Pathoge\u0301nie Bacte\u0301rienne, CNRS, URA 2172, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Agne\u0300s","family":"Dillies","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Plate-Forme 2, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Coppe\u0301e","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Plate-Forme 2, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham L.","family":"Sonenshein","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agne\u0300s","family":"Fouet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 Toxines et Pathoge\u0301nie Bacte\u0301rienne, CNRS, URA 2172, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.07.002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01780-07"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05597.x"},{"key":"e_1_3_2_6_2","first-page":"337","year":"1966","unstructured":"Bernstein, S. 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