"The etiologic agent of cholera, Vibrio cholerae, is an important cause of human morbidity and mortality, particularly in developing countries or following environmental disasters. The watery diarrhea characteristic of cholera results from the action of bacterial virulence determinants, notably cholera toxin, which gene has been acquired by horizontal gene transfer. V. cholerae as a facultative pathogen commonly occurs in aquatic ecosystems, its true habitat, where it intimately associates with phyto- and zooplankton.My proposal will investigate intensively the interaction between V. cholerae and non-vertebrate animals in marine environments and test the hypothesis that virulence determinants important in human disease are also critical for colonization of these environmental hosts. There are three interlinked specific aims:Aim 1: Establish microcosms involving V. cholerae and its environmental hosts.Aim 2: Identify factors that are beneficial for both lifestyles of V. cholerae.Aim 3: Determine the role of known virulence factors in nature.There is growing concern about the (re-)emergence of infectious agents and the threat this poses to human health particularly in the context of climate change. The sporadic and unpredictable nature of cholera epidemics has long puzzled environmental microbiologists. The interdisciplinary research proposed in this study will provide the missing link between the ecology and evolution of V. cholerae on the one hand and its pathogenesis on the other. Knowledge of how an innocuous microbe in an aquatic environment can become a major human pathogen and identification of the factors responsible are both of considerable importance."