Cross-linking teichoic acids by click chemistry prevents bacterial cell growth

This work identifies a novel antibacterial mechanism that targets the cell wall of the human pathogen Streptococcus pneumoniae. Unlike conventional cell-wall targeting antibiotics, which inhibit the natural cross-linking of peptidoglycan, we introduce artificial cross-links using metabolic engineering to insert a clickable function into the other main component of the Gram-positive cell wall, the teichoic acids, then perform Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC) and demonstrate that this results in impaired cell growth.