Metallo-β-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed β-lactam/β-lactamase inhibitor drug combination aztreonam-avibactam (ATM-AVI) have been reported. Here, we analyzed a series of 118 clinical MBL-producing E. coli isolates of various geographical origins for susceptibility to ATM-AVI. The nature of the PBP3 protein sequence and the occurrence of bla_CMY genes for susceptibility to ATM-AVI were investigated. We showed here that elevated MICs of ATM-AVI among MBL-producing E. coli isolates resulted from a combination of different features, including modification of PBP3 protein sequence through specific amino acid insertions and production of CMY-type enzymes, particularly, CMY-42. We showed here that those insertions identified in the PBP3 sequence are not considered the unique basis of resistance to ATM-AVI, but they significantly contribute to it.

中文翻译：

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遗传特征导致金属-β-内酰胺酶生产大肠杆菌分离株中对氨曲南-阿维巴坦的敏感性降低

已经报道了产生金属-β-内酰胺酶（MBL）的大肠杆菌分离株，其对新开发的β-内酰胺/β-内酰胺酶抑制剂药物组合氨曲南-avibactam（ATM-AVI）具有抗性。在这里，我们分析了来自不同地理起源的118种临床MBL生产大肠杆菌分离株对ATM-AVI的敏感性。研究了PBP3蛋白序列的性质和bla _CMY基因对ATM-AVI的敏感性。我们在这里证明了在产生MBL的大肠杆菌中ATM-AVI的MIC升高分离株是由不同特征的组合产生的，这些特征包括通过特定氨基酸插入修饰PBP3蛋白序列和产生CMY型酶（特别是CMY-42）。我们在这里表明，在PBP3序列中鉴定出的那些插入不被认为是对ATM-AVI产生抗性的唯一基础，但它们对此做出了重要贡献。