Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

Significance Human microbiota have a huge impact on health from proper development of the immune system to maintenance of normal physiological processes. The largest concentration of microbes is found in the colon, which is home to hundreds of bacterial species, most of which are obligate anaerobes. This population also poses a significant threat of opportunistic infection, and of all the species present, Bacteroides fragilis is the anaerobe most frequently isolated from extraintestinal infections of intestinal origin. The findings presented here describe a unique ability of this species to efficiently deglycosylate complex N-linked glycans from the most abundant glycoproteins found in serum and serous fluid, which gives B. fragilis a competitive, nutritional advantage for extraintestinal growth. Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. Among the Bacteroides spp. in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. This activity is mediated by an outer membrane protein complex designated as Don. Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus.