Troy Hubbard

　　Division of Microbiology and Immunobiology at Harvard Medical School and the Division of Infectious Diseases at Brigham and Women’s Hospital

　　The coupling of massively parallel sequencing technology with genomic perturbation platforms, including transposon and CRISPR-Cas9 mutagenesis, has transformed the study of host-pathogen interactions. In the Waldor lab, we utilized these powerful technologies to study the pathogenesis of Vibrio parahaemolyticus, the leading cause of seafood-borne enteritis. First, we used transposon-insertion sequencing to identify bacterial genes that allow V. parahaemolyticus to access and proliferate within the gastrointestinal tract. In doing so, we found that T3SS2, a profoundly cytotoxic and horizontally-acquired type III secretion system, is the major determinant of V. parahaemolyticus intestinal colonization. Motivated by the critical role that T3SS2 plays during intestinal colonization, we used CRISPR-Cas9 technology to identify mutations in human genes that allowed colonic epithelial cells to resist the cytotoxic activity of T3SS2. Our screen found that fucosylatedglycans, presented on the surface of human colonic epithelial cells, are critical for the function of T3SS2. Together, our studies illustrate how complementary forward genetic screens, conducted in the pathogen and the host, can reveal both the bacterial factors and host processes that underlie a host-pathogen interaction.