title: A peptidoglycan fragment triggers β-lactam resistance in Bacillus licheniformis.
abstract: To resist to β-lactam antibiotics Eubacteria either constitutively synthesize a β-lactamase or a low affinity penicillin-binding protein target, or induce its synthesis in response to the presence of antibiotic outside the cell. In Bacillus licheniformis and Staphylococcus aureus, a membrane-bound penicillin receptor (BlaR/MecR) detects the presence of β-lactam and launches a cytoplasmic signal leading to the inactivation of BlaI/MecI repressor, and the synthesis of a β-lactamase or a low affinity target. We identified a dipeptide, resulting from the peptidoglycan turnover and present in bacterial cytoplasm, which is able to directly bind to the BlaI/MecI repressor and to destabilize the BlaI/MecI-DNA complex. We propose a general model, in which the acylation of BlaR/MecR receptor and the cellular stress induced by the antibiotic, are both necessary to generate a cell wall-derived coactivator responsible for the expression of an inducible β-lactam-resistance factor. The new model proposed confirms and emphasizes the role of peptidoglycan degradation fragments in bacterial cell regulation.
authors.affiliation: Centre d'Ingénierie des Protéines, Institut de Chimie B6A, Sart-Tilman, Belgium.
authors.forename: Ana
authors.initials: A
authors.lastname: Amoroso
authors.forename: Julien
authors.initials: J
authors.lastname: Boudet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Berzigotti
authors.forename: Valérie
authors.initials: V
authors.lastname: Duval
authors.forename: Nathalie
authors.initials: N
authors.lastname: Teller
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
authors.forename: André
authors.initials: A
authors.lastname: Luxen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Simorre
authors.forename: Bernard
authors.initials: B
authors.lastname: Joris
mesh_terms: D000215:Acylation; D001407:Bacillus / Q000201:enzymology / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism; D004790:Enzyme Induction / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010406:Penicillins / Q000378:metabolism / Q000494:pharmacology; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004151:Dipeptides; D010406:Penicillins; D010457:Peptidoglycan; D044925:Oxidoreductases Acting on CH-CH Group Donors; C434934:trans-2-enoyl-CoA reductase (NADPH); C569108:BlaR1 protein, Staphylococcus aureus; D008666:Metalloendopeptidases; D001618:beta-Lactamases