title: Bacterial cell-wall recycling.
abstract: 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 β-lactamase induction. In some Gram-positive organisms, short peptides derived from the cell wall regulate the induction of both β-lactamase and β-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 β-lactams in vitro against inducible AmpC β-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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Jarrod W
authors.initials: JW
authors.lastname: Johnson
authors.forename: Jed F
authors.initials: JF
authors.lastname: Fisher
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000378:metabolism; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; C071526:AmpR protein, Bacteria; D016695:Glycosyltransferases; D009238:N-Acetylmuramoyl-L-alanine Amidase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases