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

Title(D)-Amino acid chemical reporters reveal peptidoglycan dynamics of an intracellular pathogen.
Publication TypeJournal Article
Year of Publication2013
AuthorsM Siegrist S, Whiteside S, Jewett JC, Aditham A, Cava F, Bertozzi CR
JournalACS Chem Biol
Volume8
Issue3
Pagination500-5
Date Published2013 Mar 15
ISSN1554-8937
KeywordsAlanine, Click Chemistry, Listeria monocytogenes, Molecular Conformation, Molecular Dynamics Simulation, Peptidoglycan
Abstract

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.

DOI10.1021/cb3004995
Alternate JournalACS Chem. Biol.
PubMed ID23240806
PubMed Central IDPMC3601600
Grant ListAI051622 / AI / NIAID NIH HHS / United States
R01 AI051622 / AI / NIAID NIH HHS / United States