Insights into the role of the flagellar glycosylation system in Campylobacter jejuni phage-host interactions

  • Author / Creator
    Sacher, Jessica C
  • Bacteriophages (phages) are the viruses that infect bacteria. Studying how phages interact with their hosts can inspire new ways of controlling bacterial pathogens and can highlight important facets of the biology of both organisms. Furthermore, phage-host characterization can inform exploitation of phages for therapeutics, diagnostics and research tools. Campylobacter jejuni is a deadly foodborne pathogen of humans, and its extensive surface structure glycosylation plays an important role in its virulence. In particular, C. jejuni flagella are required for colonization of its niche in the gastrointestinal tract of birds, and are also required for virulence in humans. C. jejuni devotes a substantial proportion of its genetic repertoire to flagellar biogenesis, which requires glycosylation with sialic acid-like sugars for assembly. Campylobacter phages tend to target either capsular polysaccharides or flagella, but little more than this is known about the factors governing Campylobacter phage-host interactions. My thesis describes the study of C. jejuni interactions with phages in the context of flagellar glycobiology. I found that C. jejuni phage NCTC 12673 interacts with host flagella and flagellar glycans in ways not previously described for other phage-host systems. Furthermore, this phage encodes a protein of unknown function (Gp047) with specific binding affinity for host flagellar glycans. I sought to determine how the C. jejuni flagellar glycosylation system and the NCTC 12673 phage each impact the biology of the other. I found that Gp047 inhibits growth of C. jejuni expressing flagellar acetamidino-modified pseudaminic acid glycans, that probing with Gp047 reveals previously unexplored diversity in C. jejuni flagellar glycans, and that Gp047 binding to motile, glycosylated flagella induces downregulation of pathways for cellular energy metabolism. I also found that C. jejuni pseudaminic acid biosynthesis (flagellar glycosylation) genes are required for bacteriophage NCTC 12673 infection, that a requirement for motility likely explains this dependence, and that oxidative stress sensitivity may explain the reduced ability of phage NCTC 12673 to plaque on non-motile C. jejuni mutants. Finally, I found that expression of the flagellar glycan binding protein Gp047 correlates with a lack of plaquing by phage NCTC 12673 on non-motile C. jejuni cells, providing an interesting foundation for future research. Overall, my work points toward flagellar glycosylation as an important factor affecting C. jejuni phage-host dynamics, and provides insight into the role of a flagellar glycan-binding phage protein in these interactions. These findings contribute to the fields of phage biology and bacterial glycobiology by providing insight into how a Campylobacter phage interacts with its heavily glycosylated host.

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  • Type of Item
  • Degree
    Doctor of Philosophy
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