Specific Labeling of Peptidoglycan Precursors as a Tool for Bacterial Cell Wall Studies

Abstract Wall chart: The predominant component of the bacterial cell wall, peptidoglycan, consists of long alternating stretches of aminosugar subunits interlinked in a large three‐dimensional network and is formed from precursors through several cytosolic and membrane‐bound steps. The high tolerance of the cell wall synthesis machinery allows for the use of labeled precursor derivatives to study diverse aspects of bacterial cell wall synthesis and interaction with antibiotics. magnified image Because of its importance for bacterial cell survival, the bacterial cell wall is an attractive target for new antibiotics in a time of great demand for new antibiotic compounds. Therefore, more knowledge about the diverse processes related to bacterial cell wall synthesis is needed. The cell wall is located on the exterior of the cell and consists mainly of peptidoglycan, a large macromolecule built up from a three‐dimensional network of aminosugar strands interlinked with peptide bridges. The subunits of peptidoglycan are synthesized inside the cell before they are transported to the exterior in order to be incorporated into the growing peptidoglycan. The high flexibility of the cell wall synthesis machinery towards unnatural derivatives of these subunits enables research on the bacterial cell wall using labeled compounds. This review highlights the high potential of labeled cell wall precursors in various areas of cell wall research. Labeled precursors can be used in investigating direct cell wall–antibiotic interactions and in cell wall synthesis and localization studies. Moreover, these compounds can provide a powerful tool in the elucidation of the cell wall proteome, the “wallosome,” and thus, might provide new targets for antibiotics.