UC Berkeley

While some microbial encounters can be pathogenic, most interactions between humans and microorganisms do not result in disease. Our gastrointestinal tract harbors approximately 100 trillion organisms, spanning about 1000 species that live in harmony with us. While we provide them with food and shelter, this complex intestinal bacterial community supplies essential nutrients, metabolizes indigestible compounds, protects us from pathogenic organisms and helps develop our immune system, thereby establishing a symbiotic relationship. Bacteroides are one of the most abundant bacterial genera living in the human gut and has long been a model system for studying the molecular mechanisms of commensal-host interactions. In the course of searching for surface structures that have immunomodulatory properties on the host, we serendipitously discovered a previously unknown surface protein BT1927 from Bacteroides that is capable of completely covering the surface of the bacteria by creating a tessellated surface layer. Interestingly, the formation of the entire proteinaceous capsule is controlled by inversion of a single promoter, making it phase-variable. Although only ~ 0.1% of the population produce this capsule in laboratory culture, analyzing the fecal metagenome sequence data from the Human Microbiome Project revealed that ~ 8% of the population produce a homologous capsule in humans, suggesting its significance in vivo. From a series of functional studies, we found that the BT1927-expressing subpopulation is profoundly resistant to complement-mediated killing, due in part to the BT1927-mediated blockade of C3b deposition. Our results show that the Bacteroides capsule is capable of a far greater degree of structural variation than previously known, perhaps to cope with the varying environmental conditions in the human intestine.