Quorum-sensing regulators control virulence gene expression in Vibrio cholerae

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Virulence factor production in Vibrio cholerae is environmentally regulated via the ToxR cascade.
• Quorum sensing (QS) regulates bacterial behavior in many species, but its role in V. cholerae virulence is unclear.

Purpose of the Study:

• To investigate the involvement of quorum-sensing regulators LuxO and HapR in V. cholerae virulence.
• To elucidate the regulatory relationship between LuxO, HapR, and the ToxR virulence regulon.

Main Methods:

• Utilized an infant mouse model to assess V. cholerae intestinal colonization.
• Employed gene arrays (microarrays) to profile transcriptional changes in wild-type and luxO mutant strains.
• Investigated gene expression regulation through genetic manipulation and reporter assays.

Main Results:

• A luxO mutant exhibited severe defects in small intestine colonization.
• The ToxR regulon was repressed in the luxO mutant, mediated by the negative regulator HapR.
• LuxO represses hapR expression during early log-phase growth; constitutive hapR expression blocked ToxR regulon expression.
• LuxO and HapR also influenced motility, protease production, and biofilm formation.

Conclusions:

• Quorum sensing, mediated by LuxO and HapR, plays a critical role in V. cholerae virulence.
• LuxO and HapR reciprocally regulate virulence gene expression in vivo.
• These findings reveal a novel layer of regulation for V. cholerae pathogenesis.