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Journal of Bacteriology, August 2009, p. 5044-5056, Vol. 191, No. 16
0021-9193/09/$08.00+0     doi:10.1128/JB.00406-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genetic Analysis of Activation of the Vibrio cholerae Cpx Pathway{triangledown}

Leyla Slamti{dagger} and Matthew K. Waldor*

Harvard Medical School and Brigham and Women's Hospital, Department of Medicine, Channing Laboratory, and HHMI, 181 Longwood Ave., Boston Massachusetts, 02115

Received 25 March 2009/ Accepted 6 June 2009

The Cpx two-component system is thought to mediate envelope stress responses in many gram-negative bacteria and has been implicated in the pathogenicity of several enteric pathogens. While cues that activate the Escherichia coli Cpx system have been identified, the nature of the molecular signals that stimulate this pathway is not well understood. Here, we investigated stimuli that trigger this system in Vibrio cholerae, a facultative pathogen that adapts to various niches during its life cycle. In contrast to E. coli, there was no basal activity of the V. cholerae Cpx pathway under standard laboratory conditions. Furthermore, several known stimuli of the E. coli pathway did not induce expression of this system in V. cholerae. There were no defects in intestinal growth in V. cholerae cpx mutants, arguing against the idea that this pathway promotes V. cholerae adaptation to conditions in the mammalian host. We discovered that chloride ions activate the V. cholerae Cpx pathway, raising the possibility that this signal transduction system provides a means for V. cholerae to sense and respond to alterations in salinity. We used a genetic approach to screen for mutants in which the Cpx pathway is activated. We found that mutations in genes whose products are required for periplasmic disulfide bond isomerization result in activation of the Cpx pathway, suggesting that periplasmic accumulation of proteins with aberrant disulfide bonds triggers the V. cholerae Cpx pathway.


* Corresponding author. Mailing address: Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Ave., Boston MA, 02115. Phone: (617) 525-4646. Fax: (617) 525-4660. E-mail: mwaldor{at}rics.bwh.harvard.edu

{triangledown} Published ahead of print on 19 June 2009.

{dagger} Present address: Unité de Biologie des Spirochètes, Institut Pasteur, 75015 Paris, France.


Journal of Bacteriology, August 2009, p. 5044-5056, Vol. 191, No. 16
0021-9193/09/$08.00+0     doi:10.1128/JB.00406-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.