Quadruple quorum-sensing inputs control Vibrio cholerae virulence and maintain system robustness

Area of Science:

• Microbiology
• Bacterial communication
• Quorum Sensing (QS)

Background:

• Bacteria utilize quorum sensing (QS) for cell-cell communication, regulating group behaviors via autoinducer (AI) signals.
• Vibrio cholerae employs two histidine kinases, CqsS and LuxQ, to detect AIs, controlling virulence and biofilm formation through the LuxO regulator.
• Previous studies indicated unidentified pathways activate LuxO, as CqsS and LuxQ mutants remained virulent.

Purpose of the Study:

• To identify additional signaling pathways regulating LuxO in Vibrio cholerae.
• To elucidate the complete sensory input controlling the QS circuit in V. cholerae.
• To understand the functional redundancy and robustness of the V. cholerae QS system.

Main Methods:

• Genetic analysis of V. cholerae mutants lacking specific histidine kinases.
• Phenotypic characterization of QS-proficient and QS-deficient strains.
• Assessment of LuxO activation levels and virulence factor production in different mutant backgrounds.

Main Results:

• Two novel histidine kinases, CqsR and VpsS, were identified as upstream regulators activating LuxO.
• Each of the four receptors (CqsS, LuxQ, CqsR, VpsS) confers QS proficiency and host colonization ability.
• Mutants lacking all four receptors exhibit LuxO-defective phenotypes.
• The four receptors function redundantly to prevent premature QS induction from signal perturbations.

Conclusions:

• The V. cholerae QS circuit integrates signals from four functionally redundant histidine kinases.
• This quadruple sensory input provides robustness and prevents premature QS activation due to AI fluctuations.
• The V. cholerae QS system has evolved to be refractory to sporadic autoinducer level changes.