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β-Lactam resistance development affects binding of penicillin-binding proteins (PBPs) of Clostridium perfringens to the fluorescent penicillin, BOCILLIN FL
- Park, Miseon, Sutherland, John B., Rafii, Fatemeh
- Anaerobe 2020 v.62 pp. 102179
- Clostridium perfringens, drug development, drug resistance, enzymes, fluorescence, gene overexpression, genes, molecular weight, mutants, mutation, penicillins, proteins, transcription (genetics)
- Alteration in the binding of bacterial penicillin-binding proteins (PBPs) to β-lactams is important in the development of drug resistance. The PBPs of wild type Clostridium perfringens ATCC 13124 and three β-lactam-resistant mutants were compared for the ability to bind to a fluorescent penicillin, BOCILLIN FL. The binding of the high molecular weight protein PBP1, a transpeptidase, to BOCILLIN FL was reduced in all of the resistant strains. In contrast, the binding of BOCILLIN FL to a low molecular weight protein, PBP6, a D-alanyl-d-alanine carboxypeptidase that was more abundant in all three resistant strains, was substantially increased. A competition assay with β-lactams reduced the binding of all of the PBPs, including PBP6, to BOCILLIN FL. β-Lactams enhanced transcription of the putative gene for PBP6 in both wild type and resistant strains. This is the first report showing that mutations in a high molecular weight PBP and overexpression of a low molecular weight PBP in resistant C. perfringens strains affected their binding to β-lactams.