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Environmental signals modulate ToxT-dependent virulence factor expression in Vibrio cholerae
1Department of Microbiology, University of Texas Health Science Center, San Antonio, Texas 78284-7758, USA.
Journal of Bacteriology
|February 27, 1999
Summary
Environmental signals like temperature and bile negatively regulate ToxT activity in Vibrio cholerae, controlling virulence factor expression. This prevents inappropriate timing and location of cholera toxin and toxin-coregulated pilus production.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- ToxT is a key regulator of Vibrio cholerae virulence factors, including cholera toxin (CT) and toxin-coregulated pilus (TCP).
- Environmental signals typically induce toxT transcription to initiate virulence factor expression.
- The precise mechanisms by which environmental cues modulate ToxT's transcriptional activity remain incompletely understood.
Purpose of the Study:
- To investigate whether environmental signals modulate the transcriptional activation function of ToxT.
- To determine if temperature and bile influence ToxT-dependent gene expression in Vibrio cholerae.
- To compare the regulatory responses of ToxT in Vibrio cholerae and Salmonella typhimurium.
Main Methods:
- Utilized inducible promoters to express ToxT in Vibrio cholerae.
- Assessed expression of CT and TCP under varying temperatures (30°C vs. 37°C) and bile concentrations (0.4%).
- Employed TnphoA fusions and luciferase reporter fusions (ctxAp- and tcpAp-luciferase) to measure ToxT-dependent transcription.
Main Results:
- High-level expression of CT and TCP was observed at 30°C, but significantly reduced or abolished at 37°C or with bile.
- Temperature and bile modulated the expression of six different ToxT-dependent TnphoA fusions.
- Negative regulation by temperature and bile occurred at the transcriptional level in Vibrio cholerae, confirmed by reporter gene assays.
- ToxT-dependent transcription in Salmonella typhimurium showed relative insensitivity to these environmental signals.
Conclusions:
- ToxT's transcriptional activity is directly modulated by environmental signals, specifically temperature and bile, in Vibrio cholerae.
- This represents an additional layer of complexity in the regulation of Vibrio cholerae virulence factors.
- Negative regulation of ToxT prevents the inappropriate temporal and spatial expression of virulence factors during cholera pathogenesis.