FUNCTION OF THE VIBRIO CHOLERAE RND EFFLUX SYSTEMS

PROJECT SUMMARY/ABSTRACT Cholera is an acute diarrheal disease that is caused by Vibrio cholerae. V. cholerae is a Gram-negative bacterium and facultative human pathogen that is native to aquatic ecosystems around theworld. The worldwide distribution of V. cholerae makes it a significant health threat anytime humanpopulations lack access to clean water; a fact exemplified by the ongoing cholera epidemic in Yemen.The devastating consequences of cholera combined with its ability to persist in the environment haveaccentuated the need for new therapeutic approaches to limit the epidemic spread of this disease. Werecently discovered that RND-mediated efflux is linked to V. cholerae adaptive responses. In theabsence of RND-mediated efflux unknown cell metabolites accumulate in V. cholerae can serve ascues to repress V. cholerae virulence. The overarching goal of this proposal is to identify thesemetabolites and characterize the role of the V. cholerae RND transporters in their efflux. Two specificaims are proposed. The first aim will identify the metabolites that are substrates of the RND effluxsystems. The second aim will identify regulators of the RND efflux systems and determine how themetabolites affect the expression of the RND systems. Determining the regulatory mechanisms andenvironmental cues that modulate V. cholerae adaptive responses will illuminate important aspects ofV. cholerae pathogenesis, provide a better understanding of the factors that contribute to epidemicspread, and may lead to the development of novel approaches to combat the disease cholera.