Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infection (UTI); however, treatment of UTI has been challenging due to increased antimicrobial resistance (AMR). One of the most important types of AMR is carbapenem resistance (CR). CR bacteria are known as an important threat to global public health today. Class B metallo-beta-lactamases (MBLs) are one of the major factors for resistance against carbapenems. We aimed to investigate the characteristics of UPEC isolates producing MBL. A cross-sectional study was conducted from October 2018 to December 2019 in Ahvaz; Iran. UPEC isolates were identified by biochemical and molecular methods. Metallo-beta-lactamase-producing isolates were detected using modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) tests. MBL genes, phylogenetic group, and virulence genes profile of carbapenem resistant isolates were determined. Conjugation assay and plasmid profiling were conducted to evaluate the ability of transferring of CR to other E. coli isolates. Clonal similarity of isolates were assessed using Enterobacterial intergenic repetitive element sequence (ERIC)-PCR. Among 406 UPEC isolates, 12 (2.95%) carbapenem-resistant were detected of which 11 were phenotypically MBL-producing strains. Four isolates were resistant to all investigated antimicrobial agents and were considered possible pandrug-resistant (PDR). blaNDM, blaOXA-48, blaIMP-1, and blaIMP-2 genes were found in 9, 5, 1, and 1 isolates, respectively. Among 30 virulence genes investigated, the traT, fyuA followed by fimH, and iutA with the frequency of 8 (66.7%), 8 (66.7%), 7 (58.3%), and 7 (58.3%) were the most identified genes, respectively. Siderophore production was the main virulence trait among carbapenem-resistant UPEC isolates. Except for two, all other isolates showed weak to moderate virulence index. In all recovered isolates, CR was readily transmitted via plasmids to other isolates during conjugation experiments. MBL and carbapenemase genes, especially blaNDM and blaOXA-48 are spreading rapidly among bacteria, which can be a threat to global public health. Therefore monitoring the emergence and dissemination of new AMR is necessary to continuously refine guidelines for empiric antimicrobial therapy. Understanding the mechanisms of resistance and virulence in this group of bacteria can play an effective role in providing new therapeutic methods.

中文翻译：

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产尿道致病性大肠杆菌金属-β-内酰胺酶分离株的毒力表征和克隆分析

尿路致病性大肠杆菌 (UPEC) 是尿路感染 (UTI) 的主要原因；然而，由于抗菌素耐药性 (AMR) 增加，UTI 的治疗一直具有挑战性。最重要的 AMR 类型之一是碳青霉烯类耐药性 (CR)。当今，CR 细菌被认为是对全球公共卫生的重要威胁。B 类金属-β-内酰胺酶 (MBL) 是对碳青霉烯类耐药的主要因素之一。我们旨在研究产生 MBL 的 UPEC 分离株的特征。2018 年 10 月至 2019 年 12 月在阿瓦士进行了横断面研究；伊朗。通过生化和分子方法鉴定了 UPEC 分离株。使用改进的碳青霉烯灭活方法 (mCIM) 和 EDTA-CIM (eCIM) 测试检测出金属-β-内酰胺酶分离株。MBL 基因，系统发育组，确定了耐碳青霉烯分离株的毒力基因谱。进行接合测定和质粒分析以评估将 CR 转移到其他大肠杆菌分离株的能力。使用肠杆菌基因间重复元件序列 (ERIC)-PCR 评估分离株的克隆相似性。在 406 株 UPEC 分离株中，检测到 12 株（2.95%）耐碳青霉烯，其中 11 株是表型 MBL 产生菌株。四个分离株对所有研究的抗菌药物都具有耐药性，并被认为可能具有泛耐药性 (PDR)。blaNDM、blaOXA-48、blaIMP-1 和 blaIMP-2 基因分别在 9、5、1 和 1 个分离株中被发现。在研究的 30 个毒力基因中，traT、fyuA 其次是 fimH 和 iutA，频率分别为 8 (66.7%)、8 (66.7%)、7 (58.3%) 和 7 (58.3%)，是鉴定最多的基因，分别。铁载体的产生是碳青霉烯类抗性 UPEC 分离株的主要毒力性状。除两个外，所有其他分离株均显示弱至中等毒力指数。在所有回收的分离株中，在接合实验期间，CR 很容易通过质粒传播到其他分离株。MBL 和碳青霉烯酶基因，尤其是 blaNDM 和 blaOXA-48 正在细菌中迅速传播，这可能对全球公共卫生构成威胁。因此，有必要监测新 AMR 的出现和传播，以不断完善经验性抗菌治疗的指南。了解这组细菌的耐药性和毒力机制，可以有效地提供新的治疗方法。除两个外，所有其他分离株均显示弱至中等毒力指数。在所有回收的分离株中，在接合实验期间，CR 很容易通过质粒传播到其他分离株。MBL 和碳青霉烯酶基因，尤其是 blaNDM 和 blaOXA-48 正在细菌中迅速传播，这可能对全球公共卫生构成威胁。因此，有必要监测新 AMR 的出现和传播，以不断完善经验性抗菌治疗的指南。了解这组细菌的耐药性和毒力机制，可以有效地提供新的治疗方法。除两个外，所有其他分离株均显示弱至中等毒力指数。在所有回收的分离株中，在接合实验期间，CR 很容易通过质粒传播到其他分离株。MBL 和碳青霉烯酶基因，尤其是 blaNDM 和 blaOXA-48 正在细菌中迅速传播，这可能对全球公共卫生构成威胁。因此，有必要监测新 AMR 的出现和传播，以不断完善经验性抗菌治疗的指南。了解这组细菌的耐药性和毒力机制，可以有效地提供新的治疗方法。特别是 blaNDM 和 blaOXA-48 正在细菌中迅速传播，这可能对全球公共健康构成威胁。因此，有必要监测新 AMR 的出现和传播，以不断完善经验性抗菌治疗的指南。了解这组细菌的耐药性和毒力机制，可以有效地提供新的治疗方法。特别是 blaNDM 和 blaOXA-48 正在细菌中迅速传播，这可能对全球公共健康构成威胁。因此，有必要监测新 AMR 的出现和传播，以不断完善经验性抗菌治疗的指南。了解这组细菌的耐药性和毒力机制，可以有效地提供新的治疗方法。