The rise in antibiotic-resistant bacteria is causing worldwide concerns. The urgent need for new antibacterial drugs calls for new thinking and strategies to explore novel, narrow-spectrum, and pathogen-specific antibacterial targets. Legionaminic acid (Leg) and pseudaminic acid (Pse) are nonulosonic acid carbohydrates with structural similarity to eukaryotic sialic acid, and are distributed in numerous pathogenic Gram-negative bacteria as components of cell surface-associated glycans. They are involved in the host interaction, pathogenicity, antiphage defense mechanism, and immune escape mechanism. To further explore their biological significance, we developed a synthesis of 2-acetamido-4-azidoacetamido-2,4,6-trideoxy-l-altrose (Alt-4NAz) and 2-azidoacetamido-4-acetamido-2,4,6-trideoxy-l-altrose (Alt-2NAz), among which Alt-4NAz served as an effective chemical reporter to realize bacterial Pse metabolic labeling. The effectiveness of this chemical reporter has been demonstrated in Pseudomonas aeruginosa, Vibrio vulnificus, and Acinetobacter baumannii strains. Expectedly, this strategy can provide a useful assay to detect phenotypic presence of Pse biosynthesis and screen for agents targeting this pathway.
ASJC Scopus subject areas
- Molecular Medicine