Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility inBacteroides thetaiotaomicron

Isolation of phages associated with the gut commensalBacteroides thetaiotaomicronreveals a link between cell surface structures, including phase-variable capsular polysaccharides, lipoproteins and S-layer proteins, and susceptibility to phage infection. A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact onBacteroides-phage interactions, we isolated 71Bacteroides thetaiotaomicron-infecting bacteriophages from two locations in the United States. UsingB. thetaiotaomicronstrains that express defined subsets of CPSs, we show that CPSs dictate host tropism for these phages and that expression of non-permissive CPS variants is selected under phage predation, enabling survival. In the absence of CPSs,B. thetaiotaomicronescapes bacteriophage predation by altering expression of eight distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles forBacteroidesCPSs and other cell surface structures that allow these bacteria to persist under bacteriophage predation, and hold important implications for using bacteriophages therapeutically to target gut symbionts.