A peptidoglycan fragment triggers β-lactam resistance in Bacillus licheniformis

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. © 2012 amoroso et al.