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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Bacillus / enzymology
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Bacillus / genetics*
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism
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Cell Wall / chemistry
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Cell Wall / metabolism
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DNA, Bacterial / chemistry
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DNA, Bacterial / metabolism
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Dipeptides / chemistry
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Dipeptides / metabolism
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Enzyme Induction / genetics
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Gene Expression Regulation, Bacterial / drug effects
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Gene Expression Regulation, Bacterial / genetics*
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Humans
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Metalloendopeptidases / chemistry
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Metalloendopeptidases / metabolism
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Oxidoreductases Acting on CH-CH Group Donors / chemistry
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Oxidoreductases Acting on CH-CH Group Donors / drug effects
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Oxidoreductases Acting on CH-CH Group Donors / metabolism*
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Penicillins / metabolism
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Penicillins / pharmacology
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Peptidoglycan / chemistry
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Peptidoglycan / metabolism*
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / genetics
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beta-Lactam Resistance / genetics*
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beta-Lactamases / biosynthesis
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beta-Lactamases / genetics
Substances
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Bacterial Proteins
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DNA, Bacterial
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Dipeptides
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Penicillins
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Peptidoglycan
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Oxidoreductases Acting on CH-CH Group Donors
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trans-2-enoyl-CoA reductase (NADPH)
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BlaR1 protein, Staphylococcus aureus
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Metalloendopeptidases
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beta-Lactamases