The effective treatment of infectious bacterial disesases is plagued by challenges associated with the emergence of bacterial strains that have evolved resistance to existing antibiotics. Therefore, there is an urgent need to identify more pathogen-associated targets that might be harnessed for selective treatment of bacterial infections. One long-overlooked class of molecular targets is bacterial glycoproteins. These biomolecules were once thought to be absent from bacteria, but recent work in the field of bacterial glycobiology has firmly established the synthesis of glycoproteins in bacteria. We have utlized the chemical technique metabolic glycan labeling to discover and target bacterial glycoproteins in the human pathogen Helicobacter pylori (Hp). Here we will present our findings, including the identification of 125 glycosylated proteins in Hp, the development of covalent antibiotics that target Hp based on its surface glycans, and the demonstration that metabolic labeling enables selective modification of glycans on pathogenic bacterial cells. Broadly, this work validates metabolic labeling as an effective and efficient approach to discover, study, and target bacterial glycoproteins.

Chemical tools to decipher the bacterial glycocode

251st National Meeting (2016)

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