title: Role of the murein precursor UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-diaminopimelic acid-D-Ala-D-Ala in repression of beta-lactamase induction in cell division mutants.
abstract: Certain beta-lactam antibiotics induce the chromosomal ampC beta-lactamase of many gram-negative bacteria. The natural inducer, though not yet unequivocally identified, is a cell wall breakdown product which enters the cell via the AmpG permease component of the murein recycling pathway. Surprisingly, it has been reported that beta-lactamase is not induced by cefoxitin in the absence of FtsZ, which is required for cell division, or in the absence of penicillin-binding protein 2 (PBP2), which is required for cell elongation. Since these results remain unexplained, we examined an ftsZ mutant and other cell division mutants (ftsA, ftsQ, and ftsI) and a PBP2 mutant for induction of beta-lactamase. In all mutants, beta-lactamase was not induced by cefoxitin, which confirms the initial reports. The murein precursor, UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-diaminopimelic acid-D-Ala-D-Ala (UDP-MurNAc-pentapeptide), has been shown to serve as a corepressor with AmpR to repress beta-lactamase expression in vitro. Our results suggest that beta-lactamase is not induced because the fts mutants contain a greatly increased amount of corepressor which the inducer cannot displace. In the PBP2(Ts) mutant, in addition to accumulation of corepressor, cell wall turnover and recycling were greatly reduced so that little or no inducer was available. Hence, in both cases, a high ratio of repressor to inducer presumably prevents induction.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uehara
authors.forename: James T
authors.initials: JT
authors.lastname: Park
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D016971:Citrobacter freundii / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D020558:GTP Phosphohydrolases / Q000235:genetics; D006602:Hexosyltransferases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009097:Multienzyme Complexes / Q000235:genetics; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism; D010458:Peptidyl Transferases / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; C065103:FtsA protein, Bacteria; C489310:FtsA protein, E coli; C068023:FtsQ protein, E coli; C071525:FtsZ protein, Bacteria; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D014157:Transcription Factors; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C071526:AmpR protein, Bacteria; C002225:UDP-N-acetylmuramic acid pentapeptide; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D020558:GTP Phosphohydrolases