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In the developing world, thousands of children succumb to the severe, diarrheal disease cholera each year. The Gram-negative bacterium V. cholerae is not only the agent of this pandemic disease, but also a symbiont of arthropods and a natural inhabitant of marine environments. Our laboratory focuses on the mechanisms V. cholerae uses to attach to the intestinal epithelia of arthropods and mammals and on the innate immune responses of these intestinal epithelia to the V. cholerae biofilm.
Our current research areas are described below:
1) Environmental signals that activate surface attachment. Our laboratory has identified multiple environmental signals that activate the Vibrio cholerae surface attachment in the laboratory. Some of these are also important for colonization of the arthropod and mammalian intestinal epithelia. We are currently investigating the role of these signals in colonization of the arthropod and mammalian intestine and the bacterial signal transduction cascades that are utilized by these signals.
2) The host-pathogen interaction using a Drosophila model. We have recently demonstrated that ingestion of pathogenic V. cholerae produces a lethal intestinal infection in the model arthropod Drosophila melanogaster. Furthermore, death of the fly is hastened by elaboration of cholera toxin. By utilizing the powerful genetic tools available in the fly, we have determined that programmed death of intestinal epithelial cells protects the fly against V. cholerae infection. We are currently examining the mechanism of programmed epithelial cell death, the bacterial factors that cause it, and the relevance to mammalian infection.
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