Bacterial cell wall recycling provides cytosolic muropeptides as effectors for beta-lactamase induction.

Abstract

A mechanism for bacteria to monitor the status of their vital cell wall peptidoglycan is suggested by the convergence of two phenomena: peptidoglycan recycling and beta‐lactamase induction. ampG and ampD, genes essential for beta‐lactamase regulation, are here shown to be required for recycling as well. Cells lacking either AmpG or AmpD lose up to 40% of their peptidoglycan per generation, whereas Escherichia coli normally suffers minimal losses and instead recycles 40 or 50% of the tripeptide, L‐alanyl‐D‐glutamyl‐meso‐diaminopimelic acid, from its peptidoglycan each generation. The ampG mutant releases peptidoglycan‐derived material into the medium. In contrast, the ampD mutant accumulates a novel cell wall muropeptide, 1,6‐anhydro N‐acetylmuramyl‐L‐alanyl‐D‐glutamyl‐meso‐diaminopimelic acid (anhMurNAc‐tripeptide), in its cytoplasm. This work suggests that AmpG is the permease for a large muropeptide and AmpD is a novel cytosolic N‐acetylmuramyl‐L‐alanine amidase that cleaves anhMurNAc‐tripeptide to release tripeptide, which is then recycled. These results also suggest that the phenomenon of beta‐lactamase induction is regulated by the level of muropeptide(s) in the cytoplasm, since an ampD mutation that results in beta‐lactamase expression even in the absence of a beta‐lactamase inducer coincides with accumulation of anhMurNAc‐tripeptide. The transcriptional regulator AmpR is presumably converted into an activator for beta‐lactamase production by sensing the higher level of muropeptide(s). This may be an example of a general mechanism for signaling the progress of external events such as cell wall maturation, cell division or cell wall damage.

Integrated regulatory responses of fimB to N -acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12

“…The dual control of fimB by Neu 5 Ac and GlcNAc should integrate signals from the environment with those originating within the cell. Peptidoglycan recycling may provide a means of monitoring the condition of the cell envelope (54), and fimB and GlcNAc-6-P could be part of such a regulatory circuit.…”

Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells

“…Their physiological functions are still uncertain, although they have been implicated in autolysis and/or peptidoglycan recycling (Parquet et al, 1983;Kitano et al, 1986;Goodell and Higgins, 1987;Shockman and Hö ltje, 1994). The relevance of AmiA and AmiB in peptidoglycan recycling has been questioned by the recent finding in E. coli of a muropeptide-permease, AmpG, and a cytosolic N-acetyl-muramyl-L-alanine amidase, AmpD, which apparently mediate the main recycling pathway (Park, 1993;Hö ltje et al, 1994;Jacobs et al, 1994;. Incidentally, a DNA fragment with extensive homology to E. coli ampD has also been identified in S. typhimurium (Hughes et al, 1993).…”

The β-Lactamase Gene Regulator AmpR Is a Tetramer That Recognizes and Binds the d-Ala-d-Ala Motif of Its Repressor UDP-N-acetylmuramic Acid (MurNAc)-pentapeptide

“…In the absence of ␤-lactams, UDP-MurNAc-pentapeptide binds to AmpR and causes the repression of ampC transcription (16). In contrast, disruption of PG metabolism by ␤-lactams increases the cytosolic concentration of 1,6-anhydroMurNAc-peptides, which appears to overwhelm endogenous AmpD activity and allows either the 1,6-anhydroMurNAc-tripeptide (16,17) or -pentapeptide species (7,18) to bind to AmpR. It has been proposed that these 1,6-anhydroMurNAc species competitively displace UDP-MurNAc-pentapeptide from AmpR, thus converting AmpR into an activator of ampC transcription (16,19).…”