title: Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria.
abstract: beta-lactam induction of chromosomal beta-lactamase in gram-negative bacteria requires the transcriptional regulator AmpR and the transport of murein breakdown products (muropeptides) into the cytoplasm. In vitro transcription shows that purified AmpR acts as an activator for ampC beta-lactamase synthesis. The murein precursor, UDP-MurNAc-pentapeptide, decreases AmpR-mediated transcriptional activation in vitro, but has no effect on an AmpR(G102E) mutant that mediates constitutive activation of ampC in vivo. Addition of the muropeptide, anhMurNAc-tripeptide, which accumulates in beta-lactamase-overproducing mutants, counteracts the negative effect of UDP-MurNAc-pentapeptide, restoring the innate ability of AmpR to induce ampC expression in vitro. Cytosolic intermediates of murein biosynthesis and degradation thus act antagonistically to control beta-lactamase expression, thereby operating as a cell-wall sensing device.
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: J M
authors.initials: JM
authors.lastname: Frère
authors.forename: S
authors.initials: S
authors.lastname: Normark
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D002473:Cell Wall / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018983:DNA Footprinting; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D009154:Mutation / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000502:physiology; D018440:beta-Lactam Resistance / Q000502:physiology*; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C071526:AmpR protein, Bacteria; C002225:UDP-N-acetylmuramic acid pentapeptide; C048795:AmpC beta-lactamases; D001618:beta-Lactamases