This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by van Schaik, W.
Right arrow Articles by Fouet, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Schaik, W.
Right arrow Articles by Fouet, A.

 Previous Article  |  Next Article 

Infection and Immunity, October 2009, p. 4437-4445, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00716-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Global Regulator CodY Regulates Toxin Gene Expression in Bacillus anthracis and Is Required for Full Virulence{triangledown} ,{dagger}

Willem van Schaik ,1,{ddagger},§ Alice Château,1,{ddagger} Marie-Agnès Dillies,2 Jean-Yves Coppée,2 Abraham L. Sonenshein,3 and Agnès Fouet1*

Institut Pasteur, Unité Toxines et Pathogénie Bactérienne, CNRS, URA 2172, Paris, France,1 Institut Pasteur, Plate-Forme 2, Paris, France,2 Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts3

Received 25 June 2009/ Returned for modification 22 July 2009/ Accepted 29 July 2009

In gram-positive bacteria, CodY is an important regulator of genes whose expression changes upon nutrient limitation and acts as a repressor of virulence gene expression in some pathogenic species. Here, we report the role of CodY in Bacillus anthracis, the etiologic agent of anthrax. Disruption of codY completely abolished virulence in a toxinogenic, noncapsulated strain, indicating that the activity of CodY is required for full virulence of B. anthracis. Global transcriptome analysis of a codY 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 codY mutant strain. The differences included reduced expression of the anthrax toxin genes in the mutant strain, which was confirmed by lacZ 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 atxA, as measured using an atxA-lacZ transcriptional fusion and by assaying atxA mRNA, was not significantly affected in the codY mutant. An atxA-lacZ translational fusion was also unaffected. Overexpression of atxA restored toxin component synthesis in the codY mutant strain. These results suggest that CodY controls toxin gene expression by regulating AtxA accumulation posttranslationally.

* Corresponding author. Mailing address: Unité Toxines et Pathogénie Bactérienne, Institut Pasteur, 28 rue du Dr. Roux, 75724 Cedex 15, France. Phone: 33145688654. Fax: 33145688954. E-mail: agnes.fouet{at}pasteur.fr

{triangledown} Published ahead of print on 3 August 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. N. Weiser

{ddagger} W.V.S. and A.C. have contributed equally to this work.

§ Present address: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Infection and Immunity, October 2009, p. 4437-4445, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00716-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»