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Integration host factor positively regulates virulence gene expression in Vibrio cholerae
Emily Stonehouse1, Gabriela Kovacikova, Ronald K Taylor
1Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Journal of Bacteriology
|May 6, 2008
Summary
Integration host factor (IHF) positively regulates Vibrio cholerae virulence. IHF binds the tcpA promoter, alleviating H-NS repression and enabling cholera toxin production.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Virulence gene expression in Vibrio cholerae is tightly regulated by environmental factors.
- Global regulators play a crucial role in controlling the transcriptional cascade of virulence factors.
Purpose of the Study:
- To investigate the role of integration host factor (IHF) in regulating virulence gene expression in Vibrio cholerae.
- To elucidate the mechanism by which IHF influences the expression of key virulence factors like tcpA and ctx.
Main Methods:
- Gene inactivation of IHF subunits (ihfA and ihfB).
- Gel mobility shift assays and DNase I footprinting to determine IHF binding.
- Analysis of virulence factor expression (tcpA, ctx) and toxin-coregulated pilus production.
- Site-directed mutagenesis of the IHF consensus site in the tcpA promoter.
Main Results:
- IHF positively affects virulence gene expression in V. cholerae.
- Inactivation of IHF reduced tcpA and ctx expression and cholera toxin production.
- IHF directly binds and bends the tcpA promoter at a specific consensus site.
- Mutation of the IHF site disrupted IHF binding and H-NS repressor binding.
- IHF appears to alleviate H-NS repression at the tcpA promoter.
Conclusions:
- Integration host factor (IHF) is a positive global regulator of Vibrio cholerae virulence.
- IHF directly interacts with the tcpA promoter, influencing the binding of other regulators like H-NS.
- IHF's role in alleviating H-NS repression is critical for the expression of virulence factors and cholera toxin production.
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