Bacterial pathogens of the gastrointestinal tract alter their expression profile upon ingestion by the host and activate a variety of factors enhancing colonization and virulence. However, gene silencing during infection might be as important as gene activation to achieve full colonization fitness. Thus, we developed and successfully applied a reporter technology to identify 101 in vivo repressed (ivr) genes of the bacterial pathogen Vibrio cholerae. In depth analysis of the in vivo repressed H+/Cl- transporter ClcA revealed an inverse requirement along gastrointestinal colonization. ClcA could be linked to acid tolerance response required during stomach passage, but ClcA expression is detrimental during subsequent colonization of the lower intestinal tract as it exploits the proton-motive force in alkaline environments. The study summarized in this addendum demonstrates that constitutive expression of ivr genes can reduce intestinal colonization fitness of V. cholerae, highlighting the necessity to downregulate these genes in vivo.
Keywords: Host-pathogen interactions; TRIVET; bacterial pathogenesis; cholera; colonization fitness; gene repression; in vivo gene regulation; murine model; spatiotemporal gene regulation; virlulence.