Project Summary. Vibrio cholerae is the etiological agent of the severe diarrheal disease cholera that infects hundreds of thousands of people each year. Benign V. cholerae bacteria emerge as pandemic pathogens by horizontally acquiring a specific set of genetic elements that encode all major V. cholerae virulence factors. We understand the role of these acquired elements in disease, but we do not understand what uniquely allows V. cholerae to acquire and integrate control of their actions in the first place. Our objective in this proposal is to characterize the role of the first identified Vibrio specific protein affecting the ability of V. cholerae to broadly acquire and control its virulence systems. This proposal offers a major leap forward in understanding V. cholerae specific factors that allow it to acquire, control, and maintain the genetic elements needed to transition from benign strain to pandemic pathogen. Our results are expected to have a positive vertical impact since it will further our understanding of biology that defines the potential of V. cholerae strains to become pathogenic, which will offer insights into the selective advantage of different V. cholerae strains and suggest new paths to environmental surveillance, prevention, and treatment options. ! !