Summary The microbial cell surface is a critical site of microbe-host interactions that often control infection outcomes. Here, using the infant rabbit model of cholera, which provides an abundant source of in vivo Vibrio cholerae cells and diarrheal fluid, we investigated the proteomic composition of this interface. Bulk diarrheal fluid proteomes revealed that cholera toxin accounts for the vast majority of the host proteins present during infection. We developed a surface biotinylation protocol to purify and quantify both bacterial and host proteins present on the surface of diarrheal fluid-derived V. cholerae . We found that SP-D, a toxin-dependent host protein that directly binds the V. cholerae surface, is a novel intestinal defense factor. Other V. cholerae -bound host proteins also bound distinct taxa of the murine intestinal microbiota. Proteomic investigation of the microbial surface-host interface should be a valuable tool for probing microbe-host interactions and their influence on homeostasis and infection.

Proteomic interrogation of the pathogen-host interface in cholera