Bacterial cell-wall recycling

Many Gram-negative and Gram-positive bacteria recycle a significant proportion of the peptidoglycan components of their cell walls during their growth and septation. In many-and quite possibly all-bacteria, the peptidoglycan fragments are recovered and recycled. Although cell-wall recycling is beneficial for the recovery of resources, it also serves as a mechanism to detect cell-wall-targeting antibiotics and to regulate resistance mechanisms. In several Gram-negative pathogens, anhydro-MurNAc-peptide cell-wall fragments regulate AmpC beta-lactamase induction. In some Gram-positive organisms, short peptides derived from the cell wall regulate the induction of both beta-lactamase and beta-lactam-resistant penicillin-binding proteins. The involvement of peptidoglycan recycling with resistance regulation suggests that inhibitors of the enzymes involved in the recycling might synergize with cell-wall-targeted antibiotics. Indeed, such inhibitors improve the potency of beta-lactams in vitro against inducible AmpC beta-lactamase producing bacteria. We describe the key steps of cell-wall remodeling and recycling, the regulation of resistance mechanisms by cell-wall recycling, and recent advances toward the discovery of cell-wall-recycling inhibitors.