Pathogenic species have to deal with a wide range of environments both within and outside the host and most have elaborate regulatory circuits to ensure the correct temporal and spatial expression of virulence factors. However, in most cases the primary clues used by the bacteria to determine whether they are in the host and the mechanisms by which this sensing occurs are not well understood. Vibrio cholerae is the causative agent of the potentially lethal epidemic diarrheal disease cholera. Na+ -based bioenergetics plays an important role in both the environmental and infectious phases of this organism. We recently reported the first example for an intimate connection between the expression of the main virulence factors and the sodium membrane bioenergetics in V. cholerae. It is conceivable that changes in the chemiosmotic sodium cycle are the primary signals that this organism uses to determine whether it is in the extra-host environment or the human gut. The objective of our research is the detailed molecular characterization of the observed linkage between transmembrane Na+ circulation and virulence in V. cholerae. Our experimental design is based on the combination of methods of classical membrane bioenergetics with the powerful tools of modern molecular genetics. Such an interdisciplinary approach will yield results that would be vitally important not only for the case of V. cholerae but also for the better understanding of regulation of virulence in various pathogenic microorganisms.
