Bacterial biofilm-host interaction during Vibrio cholerae infection

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DESCRIPTION (provided by applicant): Vibrio cholerae is the causative agent of cholera, an acute dehydrating diarrhea that is epidemic in many developing countries. Between epidemics, V. cholerae live in natural aquatic habitats in association with various plankton and zooplankton, often in the form of biofilms. Existence of V. cholerae in biofilms not only helps its survival in the natural environment, but enhances its infectivity as well since biofilm associated cells are resistant to the acidic stomach environment of the human host. However, upon entering the colonization sites, how V. cholerae detaches from the biofilm structure to colonize intestinal surface and how V. cholerae controls its gene expression in response to the changes in host environments is largely unknown. Our preliminary results suggest that host factor(s) are involved in the dispersal process. We thus hypothesize that upon entering upper intestines, V. cholerae biofilm-associated cells interact with host factors and change their transcriptional profiles to promote rapid dispersal from the biofilm structure, thus efficiently colonize intestinal surface and cause diseases. We will identify the chemical properties of the host biofilm detaching factors (BDF) using biochemical and chemical approaches. We will investigate how V. cholerae biofilm-associated cells respond to BDF to alter the expression of biofilm-related genes and how this leads them to accelerate their detachment. We will test the roles of BDF-response regulators played in biofilm detachments and colonization in the mouse model. We will also apply microarray analysis to investigate transcriptional changes during V. cholerae biofilm associated cells enter into mouse intestines. This research into the interaction of host factors and V. cholerae biofilms may lead to the possibility of direct manipulation of bacterial biofilm growth in vivo. Thus ultimately therapeutic treatments of biofilm associated pathogens can be developed by disrupting beneficial biofilm dispersal (as in the case of V. cholerae) or enhancing biofilm dispersal where it may be detrimental to bacterial survival (such as biofilm associated growth on catheters or various implants).PUBLIC HEALTH RELEVANCE: Vibrio cholerae has figured prominently in the history of infectious diseases as a cause of periodic global epidemics. Despite major improvements in medical treatment as well as a better understanding of the molecular processes involved in the virulence of V. cholerae, cholera still occurs widely in epidemic form particularly in South Asia, Africa, and Latin America. This study proposed will shed light on importance of V. cholerae's genetic controls in host-pathogen interactions, with the goal of better understanding V. cholerae pathogenesis and, potentially, discovering novel treatment options for the cholera disease.