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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.