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PhD Dissertation Defense: Taylor Nguyen

February 7 @ 10:00 pm - 11:00 pm

Title: Engineering the microbiome: using bacteriophages to probe the ecological dynamics of gut communities
Abstract: As associations between gut microbiome composition and various disease states are increasingly established, efforts to engineer gut communities as therapeutic solutions have accelerated. In addition to therapeutic clinical applications, phages provide exciting opportunities in basic science research to probe ecological dynamics in microbial communities. Antibiotics are typically used to remove targeted species, but they can have long-lasting, deleterious, and off-target effects. Here, we harness the lytic activity of bacteriophages (hereafter, phages), viruses that target and lyse to bacteria. We isolate novel bacteriophages to target and remove gut commensal Escherichia fergusonii (Ef) from complex, undefined stool-derived in vitro communities (SICs). We found that Ef growth is unaffected by the emergence of resistance when treated with phage in monoculture, but phage-resistant mutants that emerge in a community setting exhibited a fitness disadvantage that allowed other Proteobacteria to expand. Using a cocktail of phages, we successfully knocked out Ef from all of our complex, undefined SICs. Using these knockout communities, we showed that Ef is responsible for the community colonization resistance against Salmonella invasion. To showcase the power of phage-based species removal, we co-cultured an Ef transposon mutant library with the knockout communities to probe the genetic mechanisms of Ef survival and growth in a community setting. We found that genes related to outer membrane (OM) structure and assembly play key roles in growth in community contexts. These OM-mutants are sensitized to toxic by-products produced by another community member, highlighting the chemical warfare-based ecological interactions within gut communities. In summary, we establish that phage-based removal of a species enables the precise, controlled manipulation of community composition necessary for mechanistic study of ecological interactions within complex, undefined microbial communities.
Please contact Madelyn Bernstein for the Zoom link

Details

Date:
February 7
Time:
10:00 pm - 11:00 pm
Event Category:
Website:
https://events.stanford.edu/event/phd-dissertation-defense-taylor-nguyen

Venue

AllenX 101X