Abstract

Carbohydrate binding to lectins, carbohydrate-binding proteins, causes adhesion between bacteria and host cells. Bacteria contain hair-like structures on the cell’s outer surface with lectins that adhere to specific glycans found on the host cell. The specificity of this interaction is influenced by the unique pattern of hydrogen bonding between the glycan and lectins. This adhesion interaction initiates biofilm formation, the accumulation of bacteria in stationary communities, which causes an increase in antibiotic resistance. By disarming bacteria, rather than killing them with antibiotics, bacterial infections can be treated with a decreased possibility of bacteria becoming resistant. The development of modified carbohydrates that can act as ligands to bind effectively to lectins could therefore inhibit biofilm formation and make bacteria easier to treat. GafD is a lectin on enterotoxigenic Escherichia coli pili that binds to N-acetylglucosamine (GlcNAc). Molecules with modifications to GlcNAc are being synthesized as inhibitors of GafD-mediated adhesion. Currently, GlcNAc derivatives 1,6-hexanediol have been successfully synthesized to incorporate additional hydrogen bonding groups. This modified molecule was tested by an enzyme-linked immunosorbent assay (ELISA) that detects and measures ligand binding. In addition, GlcNAc derivatives with aromatic groups, including 1,4-Benzenedimethano and 4-Hydroxybenzyl, are being synthesized to provide a better understanding of their interactions with aromatic amino acids in the binding site. By developing a variety of modified carbohydrates, we aim to gain a deeper understanding of the properties involved in creating a high-affinity inhibitor for E. coli adhesion.

Keywords

antibiotic resistance, N-acetylglucosamine, enterotoxigenic E. coli, Adhesion Inhibitors

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