Year of Graduation

2024

Level of Access

Restricted Access Thesis

Embargo Period

5-16-2024

Department or Program

Biochemistry

First Advisor

Danielle Dube

Abstract

The rise of antibiotic-resistant bacteria is becoming a global health threat, necessitating the discovery of new antibiotics. Bacterial glycans, a dense array of carbohydrates on the surface of bacteria, are a great antibiotic target because of their distinctive bacteria-specific structures and their ties to bacterial fitness and function. Metabolic inhibitors acting as substrate decoys can disrupt proper bacterial glycan biosynthesis and potentially form the basis of new antibiotics. O-glycosides based on bacterial monosaccharides are effective and selective inhibitors of bacteria glycan biosynthesis in the gastric pathogen Helicobacter pylori. Building on previous work in our lab, we crafted 2-naphthalenemethanol (O-NAP) glycosides based on rare bacterial monosaccharide scaffolds. We explored their ability to inhibit glycan biosynthesis in the pathogenic bacteria Helicobacter pylori, in the commensal gut bacteria Bacteroides fragilis, and in mammalian cells. We found that Fuc-O-NAP disrupts glycoprotein biosynthesis and various fitness attributes in H. pylori. This study demonstrates that Fuc-O-NAP is a more potent glycosylation inhibitor than previously reported O-benzyl or S-benzyl analogs while maintaining selectivity against commensal bacteria.

Restricted

Available only to users on the Bowdoin campus.

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