(D)-Amino acid chemical reporters reveal peptidoglycan dynamics of an intracellular pathogen

ACS Chem Biol. 2013 Mar 15;8(3):500-5. doi: 10.1021/cb3004995. Epub 2013 Jan 11.


Peptidoglycan (PG) is an essential component of the bacterial cell wall. Although experiments with organisms in vitro have yielded a wealth of information on PG synthesis and maturation, it is unclear how these studies translate to bacteria replicating within host cells. We report a chemical approach for probing PG in vivo via metabolic labeling and bioorthogonal chemistry. A wide variety of bacterial species incorporated azide and alkyne-functionalized d-alanine into their cell walls, which we visualized by covalent reaction with click chemistry probes. The d-alanine analogues were specifically incorporated into nascent PG of the intracellular pathogen Listeria monocytogenes both in vitro and during macrophage infection. Metabolic incorporation of d-alanine derivatives and click chemistry detection constitute a facile, modular platform that facilitates unprecedented spatial and temporal resolution of PG dynamics in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Alanine / metabolism*
  • Click Chemistry
  • Listeria monocytogenes / chemistry
  • Listeria monocytogenes / cytology
  • Listeria monocytogenes / metabolism*
  • Molecular Conformation
  • Molecular Dynamics Simulation*
  • Peptidoglycan / biosynthesis
  • Peptidoglycan / chemistry
  • Peptidoglycan / metabolism*


  • Peptidoglycan
  • Alanine