Advisor: Eric Martens, Ph.D.
Research into the function of the human gut microbiome has transformed our understanding of the microbiology that exists within us. Bacteriophages are among the most prevalent biological entities in the gut and play roles beyond infecting bacteria, like modulating host immunity. My work will help understand how the common human gut symbiont, Bacteroides thetaiotaomicron (Bt), persists despite constant pressure by bacteriophages. We have identified >70 different bacteriophages and demonstrated that Bt is equipped with 19 different phase-variable systems used to resist eradication by bacteriophages. These systems include 8 surface capsular polysaccharides (CPS) and 8 members of a new family of surface layer (S-layer) proteins, which switch on or off to pre-adapt some Bt cells to challenges. Regulation of specific S-layer proteins is correlated with deletion of a high-affinity B12 receptor and concentration of B12 in vitro. I have also demonstrated that co-inoculation of Bt with one bacteriophage in mice enables both bacterium and virus to coexist for over two months, presumably because infection selects for resistant Bt cells and phase-variation reverts some cells to be susceptible, allowing bacteriophage to replenish. I hypothesize that each of these systems mediates optimal protection against specific bacteriophages and that S-layers and other resistance mechanisms provide conditional advantages based on available nutrients. These findings provide insight to how bacterial prey can coexist with their predator bacteriophage, which may clarify how and why changes in the phage “virome” have been associated with diseases like inflammatory bowel disease.