UC Riverside

V. cholerae is a Gram-negative enteric pathogen that can cause severe watery diarrhea in human, which affects millions of people in developing countries each year. The gut microbiota that is recognized as a factor in driving susceptibility to the infection, has evolved a variety of strategies to restrict pathogen growth, including nutrient competition, stimulating host immunity, regulation of virulence gene expression, and direct killing. Diet plays a dominant role in shaping the gastrointestinal environment and the function of the gut microbiota. It also regulates the infection of pathogens as well as the interactions between pathogens and gut microbiota. Here, we explored the interspecies competition by direct killing between the gut commensal Escherichia coli and V. cholerae. We identified the genotoxicity of E. coli-produced colibactin toward V. cholerae and other gut microbial commensals. We also demonstrated that dietary proteins regulate V. cholerae colonization and competition against the colibactin-producing E. coli via type VI secretion system. In addition, we showed that gut microbial community regulates host hydrogen peroxide production and V. cholerae resistance to oxidative stress. Combining next generation sequencing analysis with mouse model and traditional molecular techniques provides more comprehensive understanding of host-microbiota-pathogen interactions, which offers new strategies in the design of prophylactic and therapeutic measures to improve global health.