Transpeptidation reinforces the structure of cell wall peptidoglycan, an extracellular heteropolymer that protects bacteria from osmotic lysis. The clinical success of transpeptidase-inhibiting β-lactam antibiotics suggests that the linkages are essential for cell wall integrity, but the presence of multiple, functionally-redundant transpeptidases in many bacterial species makes it challenging to determine crosslink function precisely. Here we present a technique to covalently link peptide strands by chemical rather than enzymatic reaction. We employ bio-compatible click chemistry to induce triazole formation between azido- and alkynyl-D-alanine residues that are metabolically installed in the cell wall of Gram-positive or Gram-negative bacteria. Synthetic triazole crosslinks can be visualized by replacing azido-D-alanine with azidocoumarin-D-alanine, an amino acid derivative that undergoes fluorescent enhancement upon reaction with terminal alkynes. Cell wall stapling protects <i>Escherichia coli</i>from β-lactam treatment. Chemical control of cell wall structure in live bacteria can provide functional insights that are orthogonal to those obtained by genetics.

Bacterial peptidoglycan stapling with functionalized D-amino acids

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.