A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria

Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine protease fragipain (Fpn), which is also encoded in B. fragilis strains that lack BFT. In this report, we identify a secreted antibacterial protein (fragipain-activated bacteriocin 1 [Fab1]) and its cognate immunity protein (resistance to fragipain-activated bacteriocin 1 [RFab1]) in enterotoxigenic and nontoxigenic strains of B. fragilis. Although BFT and Fab1 share no sequence identity, Fpn also activates the Fab1 protoxin, resulting in its secretion and antibacterial activity. These findings highlight commonalities between host- and bacterium-targeting toxins in intestinal bacteria and suggest that antibacterial antagonism may promote the conservation of pathways that activate host-targeting virulence factors.