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Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification
Senlian Hong1, Yujie Shi1, Nicholas C Wu2
1Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Nature Communications
|April 19, 2019
Summary
Chemoenzymatic modification enables precise control of cell surface glycans. Increased sialyl Lewis X (sLeX) on host cells enhances influenza A virus (IAV) killing, linked to specific hemagglutinin interactions.
Area of Science:
- Glycobiology
- Virology
- Enzymology
Background:
- Metabolic oligosaccharide engineering is one approach to modify cell surface glycans.
- Chemoenzymatic modification offers a complementary strategy for glycan engineering.
Purpose of the Study:
- To identify efficient enzymes for live-cell glycan modification.
- To develop a host-cell-based assay for probing glycan-mediated influenza A virus (IAV) infection.
- To investigate the role of specific glycans in IAV pathogenesis.
Main Methods:
- Utilized Pasteurella multocida α2-3-sialyltransferase M144D mutant, Photobacterium damsela α2-6-sialyltransferase, and Helicobacter mustelae α1-2-fucosyltransferase for chemoenzymatic modification.
- Combined these enzymes with Helicobacter pylori α1-3-fucosyltransferase to create a host-cell-based assay.
- Tested the assay with wild-type and mutant strains of H1N1 and H3N2 influenza A viruses.
Main Results:
- Identified specific sialyltransferases and fucosyltransferases as effective tools for live-cell glycan modification.
- Demonstrated a positive correlation between high Neu5Acα2-6Gal levels and IAV-induced host-cell death, dependent on hemagglutinin (HA) binding affinity.
- Observed that increased sialyl Lewis X (sLeX) on host cells exacerbated killing by several IAV strains, including a mutant HK68-MTA.
- Proposed a structural basis for enhanced killing involving a putative hydrogen bond between HA-HK68-MTA Trp222 and the α1-3-linked fucose of sLeX.
Conclusions:
- Chemoenzymatic glycan modification is a powerful tool for studying host-pathogen interactions.
- Specific glycan structures, such as Neu5Acα2-6Gal and sLeX, significantly influence IAV infectivity and pathogenicity.
- Structural features of viral hemagglutinin play a critical role in mediating glycan-dependent host cell damage.
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