Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin

Microcins are small antibacterial proteins that mediate interbacterial competition. Their narrow-spectrum activity provides opportunities to discover microbiome-sparing treatments. However, microcins have been found almost exclusively in Enterobacteriaceae. Their broader existence and potential implications in other pathogens remain unclear. Here, we identify and characterize a microcin active against pathogenic Vibrio cholerae: MvcC. We show that MvcC is reliant on the outer membrane porin OmpT to cross the outer membrane. MvcC then binds the periplasmic protein OppA to reach and disrupt the cytoplasmic membrane. We demonstrate that MvcC’s cognate immunity protein is a protease, which precisely cleaves MvcC to neutralize its activity. Importantly, we show that MvcC is active against diverse cholera isolates and in a mouse model of V. cholerae colonization. Our results provide a detailed analysis of a microcin outside of Enterobacteriaceae and its potential to influence V. cholerae infection.