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Journal of Bacteriology, March 1999, p. 1508-1514, Vol. 181, No. 5
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Environmental Signals Modulate ToxT-Dependent Virulence Factor Expression in Vibrio cholerae

Darren A. Schuhmacher and Karl E. Klose*

Department of Microbiology, University of Texas Health Science Center, San Antonio, Texas 78284-7758

Received 11 November 1998/Accepted 14 December 1998

The regulatory protein ToxT directly activates the transcription of virulence factors in Vibrio cholerae, including cholera toxin (CT) and the toxin-coregulated pilus (TCP). Specific environmental signals stimulate virulence factor expression by inducing the transcription of toxT. We demonstrate that transcriptional activation by the ToxT protein is also modulated by environmental signals. ToxT expressed from an inducible promoter activated high-level expression of CT and TCP in V. cholerae at 30°C, but expression of CT and TCP was significantly decreased or abolished by the addition of 0.4% bile to the medium and/or an increase of the temperature to 37°C. Also, expression of six ToxT-dependent TnphoA fusions was modulated by temperature and bile. Measurement of ToxT-dependent transcription of genes encoding CT and TCP by ctxAp- and tcpAp-luciferase fusions confirmed that negative regulation by 37°C or bile occurs at the transcriptional level in V. cholerae. Interestingly, ToxT-dependent transcription of these same promoters in Salmonella typhimurium was relatively insensitive to regulation by temperature or bile. These data are consistent with ToxT transcriptional activity being modulated by environmental signals in V. cholerae and demonstrate an additional level of complexity governing the expression of virulence factors in this pathogen. We propose that negative regulation of ToxT-dependent transcription by environmental signals prevents the incorrect temporal and spatial expression of virulence factors during cholera pathogenesis.

* Corresponding author. Mailing address: Dept. of Microbiology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284-7758. Phone: (210) 567-3990. Fax: (210) 567-6612. E-mail: klose{at}uthscsa.edu.

Journal of Bacteriology, March 1999, p. 1508-1514, Vol. 181, No. 5
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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