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Vibrio cholerae causes a dehydrating diarrheal illness that can be rapidly fatal in the absence of specific treatment. The organism is an historic scourge and, like similar infectious diseases, may have influenced the evolution of the human genome. We report here the results of the first candidate gene association study of cholera. In a family-based study of 76 pedigrees from Dhaka, Bangladesh, we evaluated the association between cholera and five candidate genes -- the cystic fibrosis transmembrane receptor; lactoferrin; long palate, lung and nasal epithelium clone 1 (LPLUNC1); estrogen related receptor alpha; and calcium activated chloride channel 1. We found a significant association with a marker in the promoter region of LPLUNC1 (rs11906665), a member of a family of evolutionarily conserved innate immunity proteins. A previous microarray-based study of duodenal biopsies revealed significantly increased expression of LPLUNC1 in cholera patients compared to healthy control subjects. Our results suggest that variation in host innate immune responses may influence the outcome of exposure to V. cholerae in an endemic setting.

An effective vaccine for Vibrio cholerae is not yet available for use in the developing world, where the burden of cholera disease is highest. Characterizing the proteins that are expressed by V. cholerae in the human host environment may provide insight into the pathogenesis of cholera and assist with the development of an improved vaccine. We analyzed the V. cholerae proteins present in the stools of 32 patients with clinical cholera. The V. cholerae outer membrane porin, OmpU, was identified in all of the human stool samples, and many V. cholerae proteins were repeatedly identified in separate patient samples. The majority of V. cholerae proteins identified in human stool are involved in protein synthesis and energy metabolism. A number of proteins involved in the pathogenesis of cholera, including the A and B subunits of cholera toxin and the toxin-coregulated pilus, were identified in human stool. In a subset of stool specimens, we also assessed which in vivo expressed V. cholerae proteins were recognized uniquely by convalescent-phase as opposed to acute-phase serum from cholera patients. We identified a number of these in vivo expressed proteins as immunogenic during human infection. To our knowledge, this is the first characterization of the proteome of a pathogenic bacteria recovered from a natural host.