Metabolic flexibility and an unusual route for peptidoglycan muramic acid recycling in mycobacteria.

biosynthesis of cell wall peptidoglycan is essential for bacterial viability under many growth conditions and is a well-validated antibiotic target. Although generally not essential for bacterial fitness under standard laboratory growth conditions, peptidoglycan recycling can aid bacterial survival under host or antibiotic stress. Peptidoglycan consists of alternating sugars-acetylmuramic acid (MurAc) and-acetylglucosamine (GlcAc) cross-linked by peptides. Recycling of these sugars can proceed via GlcAc and glucosamine intermediates (-type) or, in the case of MurAc, bypass these intermediates altogether (-type). We serendipitously discovered that the pathogenand model organismassimilate 2-modified MurAc probes into their peptidoglycan despite lacking the-type machinery that is normally required for incorporation of these molecules. Our data suggest that unmodified and 2-modified MurAc incorporate intopeptidoglycan via multiple pathways, the former preferentially via an-type route and the latter preferentially via a non-, non--type route with GlcAc but not glucosamine intermediates. These findings reveal metabolic flexibility in mycobacterial cell wall recycling that encompasses a previously undescribed pathway.