IMPACT OF PHAGES ON VIBRIO CHOLERAE INFECTION AND THEIR USE IN PREVENTING CHOLERA

The factors that govern the spread of Vibrio cholerae remain ill-defined. By studying cholera patient rice-water stools in Bangladesh and Haiti we found that most cholera patients shed high titers of at least one of three distinct species of virulent phage. We provide evidence that these phages prey extensively on V. cholerae within the human gastrointestinal tract, thus impacting the infection, spread and evolution of V. cholerae. We have begun to reveal the biology of these phages and details of the arms race between each phage and V. cholerae. We have shown that LPS and OmpU serve as receptors for these phages. Phage-resistant escape mutants, deficient in these receptors, are rendered avirulent. By combining these phages we have developed a cocktail that, when administered to animals up to 24 hours prior to challenge, can prevent cholera. The combination of phages appears to largely prevent the appearance of mutants that can escape predation by all three phages. Ongoing studies seek to determine the frequency, or lower bound, at which escape mutants to the phage cocktail arise, as well as the impact, if any, of the phage cocktail on the gut microbiota in healthy animals.