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Pett, Nicola Jacqueline

University of British Columbia

Bacteriophages (phages) are viruses that infect bacteria with species- and strain-level specificity and are the most abundant biological entities across all known ecosystems. Within bacterial communities, such as those found in the gut microbiota, phages are implicated in regulating microbiota population dynamics and driving bacterial evolution. The specificity of phage-bacterial interactions has generated renewed interest in phage research as a potential alternative strategy to counter the increasing threat of antimicrobial resistant bacteria. While there has been some success in using phage therapy to combat bacterial septic infections, we still do not have the foundational understanding of phage-bacteria-host dynamics within our gut ecosystems that is needed for their safe development. Recent studies demonstrating that phages adhere to intestinal mucus through specific capsid proteins (Hoc) have suggested that phages may protect the underlying epithelium from bacterial invasion, providing a host-extrinsic mechanism to maintain intestinal homeostasis. Here, I build upon these findings to investigate the kinetics between Escherichia bacteriophage T4 (containing a Hoc domain) and its target bacterium, Escherichia coli, within the intestinal tract of a gnotobiotic mouse model. I determined that T4 phage and E. coli can stably coexist within the murine gastrointestinal tract in the absence of other microbes, despite continual phage predation. However, I was unable to conclude that T4 phage retention within the murine gut requires Hoc protein-mediated mucus adhesion. Further, my data suggest that gut-colonising T4 phage elicit a type 1 immune response in the gut-draining lymph nodes, without causing inflammatory disease. Together, these results suggest that T4 phage is well tolerated in the gastrointestinal tract of gnotobiotic mice by the bacterial and metazoan hosts and may contribute to immune system priming.

Text

2024-01-04

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87075

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/