Christi L McElheny, Erika L Butcher, Akito Kawai, Robert M Q Shanks, Ryan K Shields, Yohei Doi
{"title":"编码青霉素结合蛋白2的mrdA单突变导致产ndm的大肠杆菌耐药的体外进化","authors":"Christi L McElheny, Erika L Butcher, Akito Kawai, Robert M Q Shanks, Ryan K Shields, Yohei Doi","doi":"10.1128/aac.01014-25","DOIUrl":null,"url":null,"abstract":"<p><p>Durlobactam, a diazabicyclooctane β-lactamase inhibitor, exhibits direct antibacterial activity by binding to penicillin-binding protein 2 (PBP2). We generated a mutant strain of New Delhi metallo-β-lactamase-producing <i>Escherichia coli</i> with a durlobactam minimum inhibitory concentration of 2 µg/mL, representing a 16-fold increase from baseline, by exposing it to increasing concentrations of durlobactam. Resistance was attributed to a point mutation in the <i>mrdA</i> gene, resulting in a V522I substitution in PBP2.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0101425"},"PeriodicalIF":4.5000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>In vitro</i> evolution of durlobactam resistance in NDM-producing <i>Escherichia coli</i> due to a single mutation in <i>mrdA</i> encoding penicillin-binding protein 2.\",\"authors\":\"Christi L McElheny, Erika L Butcher, Akito Kawai, Robert M Q Shanks, Ryan K Shields, Yohei Doi\",\"doi\":\"10.1128/aac.01014-25\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Durlobactam, a diazabicyclooctane β-lactamase inhibitor, exhibits direct antibacterial activity by binding to penicillin-binding protein 2 (PBP2). We generated a mutant strain of New Delhi metallo-β-lactamase-producing <i>Escherichia coli</i> with a durlobactam minimum inhibitory concentration of 2 µg/mL, representing a 16-fold increase from baseline, by exposing it to increasing concentrations of durlobactam. Resistance was attributed to a point mutation in the <i>mrdA</i> gene, resulting in a V522I substitution in PBP2.</p>\",\"PeriodicalId\":8152,\"journal\":{\"name\":\"Antimicrobial Agents and Chemotherapy\",\"volume\":\" \",\"pages\":\"e0101425\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antimicrobial Agents and Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1128/aac.01014-25\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antimicrobial Agents and Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/aac.01014-25","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
In vitro evolution of durlobactam resistance in NDM-producing Escherichia coli due to a single mutation in mrdA encoding penicillin-binding protein 2.
Durlobactam, a diazabicyclooctane β-lactamase inhibitor, exhibits direct antibacterial activity by binding to penicillin-binding protein 2 (PBP2). We generated a mutant strain of New Delhi metallo-β-lactamase-producing Escherichia coli with a durlobactam minimum inhibitory concentration of 2 µg/mL, representing a 16-fold increase from baseline, by exposing it to increasing concentrations of durlobactam. Resistance was attributed to a point mutation in the mrdA gene, resulting in a V522I substitution in PBP2.
期刊介绍:
Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.