A proteolytically activated antimicrobial toxin encoded on a mobile plasmid of Bacteroidales induces a protective response

Phocaeicola vulgatus is one of the most abundant and ubiquitous bacterial species of the human gut microbiota, yet a comprehensive analysis of antibacterial toxin production by members of this species has not been reported. Here, we identify and characterize a previously undescribed antibacterial protein. This toxin, designated BcpT, is encoded on a small mobile plasmid that is largely confined to strains of the closely related species Phocaeicola vulgatus and Phocaeicola dorei . BcpT is unusual in that it requires cleavage at two distinct sites for activation, and we identify bacterial proteases that perform this activation. We further identify BcpT’s receptor as the Lipid A-core glycan, allowing BcpT to target species of other Bacteroidales families. Exposure of cells to BcpT induces a response involving an unusual sigma/anti-sigma factor pair that is likely triggered by cell envelope stress, resulting in the expression of genes that partially protect cells from multiple antimicrobial toxins. The bacterium Phocaeicola vulgatus is commonly found in the human gut. Here, the authors show that the microorganism produces an antibacterial toxin that targets the LPS core glycan of closely related species and induces a response that partially protects cells from multiple antimicrobial toxins.