Survival in a cruel world: How Vibrio cholerae and Salmonella respond to an unwilling host

V. cholerae and Salmonella are paradigms of extracellular and intracellular enteric pathogens. S. typhimurium has been a workhorse of bacterial genetics for many years, providing a sophisticated set of genetic tools for construction and analysis of mutants. In contrast, V. cholerae only recently has become amenable to genetic analysis. Despite this disparity in genetic tools, the basis of V. cholerae virulence is better understood than S. typhimurium virulence because of the additional mechanistic complexity necessary for intracellular pathogenesis. Both V. cholerae and Salmonella have evolved an exquisitely refined molecular choreography to express the right genes at the right time and in the right place to facilitate infection of the host. Although many virulence factors have been identified in both these enteric pathogens, there remain gaping holes in our knowledge of both the virulence genes and regulatory genes required for pathogenesis. Understanding the regulation of virulence genes may provide insight into conditions a pathogen encounters upon infection, thus providing an approach for identifying other virulence genes. Once the regulatory signals are identified, dissecting the details of the regulatory mechanism may give further clues to the mechanism of virulence and may identify new targets for antimicrobial agents. It is noteworthy that despite the wealth of elegant research on V. cholerae and Salmonella, we are still far from fully understanding their virulence from either the pathogen or host perspective. Moreover, these are just two examples from a countless number and variety of important bacterial pathogens.