Fig. 1. Role of AmpG in peptidoglycan recycling and antibiotic resistance.

a Under physiological conditions, mature PG is processed into GlcNAc-1,6-anhydroMurNAc peptides (primarily tetrapeptides) that are transported across the bacterial inner membrane to the cytosol by AmpG for recycling. An intermediate in this normal PG biosynthetic pathway, UDP-MurNAc-pentapeptide, binds to AmpR, which represses production of the class C β-lactamase AmpC. However, in the presence of β-lactams, inhibition of PBPs leads to an accumulation of hydrolyzed PG pentapeptide fragments, which are transported to the cytosol by AmpG, converted to 1,6-anhydroMurNAc-pentapeptides by NagZ, bind AmpR and induce expression of ampC. Secreted AmpC hydrolyzes β-lactams, providing antibiotic resistance¹⁰. b Chemically synthesized GlcNAc-1,6-anhydroMurNAc derivatives made for this study.