Discovery and Characterization of an Antimicrobial Toxin of the Gut Symbiont Bacteroides fragilis

Abstract

The gut microbiota represents one of most densely populated ecosystems on earth. The trillions of bacteria that populate the gastrointestinal tract carry out essential tasks for the host, such as harvesting energy from food, synthesizing micronutrients, and participating in the development of the immune system. Gut bacteria are also implicated in disease, with certain bacteria linked to inflammatory diseases, obesity and depression. Given the significance of the gut microbiota, understanding the factors that shape this complex ecosystem is of great scientific importance. One of the underappreciated forces that shapes the gut microbiota is antagonism: the process by which species kill or otherwise interfere with other species. Previous work in the Comstock group showed that the gut symbiotic bacterium Bacteroides fragilis 638R produces two diffusible toxins that each kill a subset of other strains of B. fragilis. I have shown that B. fragilis 638R produces a third toxin, BSAP-4, that kills a different subset of strains of B. fragilis. I characterized the activity of this toxin by demonstrating its activity spectrum and quantifying its killing behavior. I identified the toxin’s receptors in target strains and bioinformatically analyzed the distribution of the toxin and its receptors in natural microbiotas. Finally, I used gnotobiotic mouse models of gut colonization to observe the fitness benefits conferred by the toxin and receptor genes.