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.

细菌青霉素结合蛋白（PBPs）与β-内酰胺的结合改变对耐药性的发展很重要。比较了野生型产气荚膜梭菌ATCC 13124和三个β-内酰胺抗性突变体的PBP与荧光青霉素BOCILLIN FL结合的能力。在所有抗性菌株中，高分子量蛋白PBP1（一种转肽酶）与BOCILLIN FL的结合都减少了。相反，BOCILLIN FL与低分子量蛋白质PBP6，D-丙氨酰-d的结合在所有三个抗性菌株中更丰富的-丙氨酸羧肽酶大大增加。用β-内酰胺进行竞争分析可降低所有PBP（包括PBP6）与BOCILLIN FL的结合。β-内酰胺在野生型和耐药菌株中均增强了PBP6推定基因的转录。这是第一个报道，表明在抗性产气荚膜梭菌菌株中高分子量PBP的突变和低分子量PBP的过表达影响了它们与β-内酰胺的结合。