Year of Graduation


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Restricted Access Thesis

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First Advisor

Danielle Dube


Helicobacter pylori is a gram-negative disease-causing bacterium that been linked to gastric carcinoma, and infection often leads to chronic gastritis and ulcers that can last for a lifetime if left untreated. Current efforts to cure H. pylori infection require “triple therapy”. There is an urgent need for new therapeutics as increasing resistance to triple therapy has developed. H. pylori’s cell surface is decorated with highly ordered glycan structures containing unique monosaccharide building blocks that are critical for its virulence, therefore, bacterial glycans are attractive therapeutic targets. However, the genes responsible for the biosynthesis of glycosylated proteins and lipids in H. pylori are not fully known nor characterized. Recent work in our laboratory has shown that glycoprotein and glycolipid biosynthesis appear to occur via a shared lipid-carrier-mediated pathway that bifurcates. Therefore, in this study, we probed our working model of glycoprotein biosynthesis via construction of glycosylation mutants coupled to metabolic oligosaccharide engineering (MOE) to study glycan production. Our results identify additional genes involved in glycolipid and glycoprotein biosynthesis and allowed us to refine our working model of these overlapping pathways. Ultimately, this work has the potential to reveal targets for glycan-based antimicrobial interference strategies.


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