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在一株来自阿拉伯联合酋长国的临床分离大肠埃希菌中发现的新型新德里金属β-内酰胺酶():抗菌药物耐药性方面的一个新挑战

Novel Variant of New Delhi Metallo-Beta-Lactamase () Discovered in a Clinical Strain of from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance.

作者信息

Al-Marzooq Farah, Ghazawi Akela, Allam Mushal, Collyns Timothy, Saleem Aqeel

机构信息

Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.

Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.

出版信息

Antibiotics (Basel). 2024 Dec 2;13(12):1158. doi: 10.3390/antibiotics13121158.

Abstract

Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of a novel variant of New Delhi metallo-β-lactamase () in from the United Arab Emirates (UAE), including its genetic context and relationship to global strains. NDM-60-producing was isolated from a rectal swab during routine screening. Characterization involved whole-genome sequencing, antimicrobial susceptibility testing, and comparative genomic analysis with 66 known NDM variants. Core genome analysis was performed against 42 global strains, including the single other reported NDM-60-positive isolate. The strain demonstrated extensive drug resistance, including resistance to novel β-lactam/β-lactamase inhibitor combinations, notably taniborbactam. NDM-60 differs from the closely related NDM-5 by a single amino acid substitution (Asp202Asn) and two amino acid substitutions (Val88Leu and Met154Leu) compared to NDM-1. NDM-60 is located on a nonconjugative IncX3 plasmid. The strain belongs to sequence type 940 (ST940). Phylogenetic analysis revealed high diversity among the global ST940 strains, which carry a plethora of resistance genes and originated from humans, animals, and the environment from diverse geographic locations. NDM-60 emergence in the UAE represents a significant evolution in carbapenemase diversity. Its presence on a nonconjugative plasmid may limit spread; however, its extensive resistance profile is concerning. Further studies are needed to determine the prevalence, dissemination, and clinical impact of NDM-60. NDM evolution underscores the ongoing challenge in managing antimicrobial resistance and the critical importance of vigilant molecular surveillance. It also highlights the pressing demand to discover new antibiotics to fight resistant bacteria.

摘要

碳青霉烯类耐药性对健康构成重大威胁。本研究报告了在来自阿拉伯联合酋长国(阿联酋)的肺炎克雷伯菌中首次检测到一种新型新德里金属β-内酰胺酶(NDM)变体并对其进行了特征分析,包括其基因背景以及与全球菌株的关系。产NDM-60的肺炎克雷伯菌是在常规筛查期间从直肠拭子中分离出来的。特征分析包括全基因组测序、抗菌药物敏感性测试以及与66种已知NDM变体的比较基因组分析。针对42株全球肺炎克雷伯菌菌株进行了核心基因组分析,包括另一株已报道的NDM-60阳性分离株。该菌株表现出广泛的耐药性,包括对新型β-内酰胺/β-内酰胺酶抑制剂组合(尤其是他尼硼巴坦)耐药。与密切相关的NDM-5相比,NDM-60有一个氨基酸替换(Asp202Asn);与NDM-1相比,有两个氨基酸替换(Val88Leu和Met154Leu)。NDM-60位于一个非接合性IncX3质粒上。该菌株属于序列型940(ST940)。系统发育分析显示全球ST940菌株具有高度多样性,这些菌株携带大量耐药基因,起源于不同地理位置的人类、动物和环境。NDM-60在阿联酋的出现代表了碳青霉烯酶多样性的重大演变。它存在于非接合性质粒上可能会限制传播;然而,其广泛的耐药谱令人担忧。需要进一步研究以确定NDM-60的流行情况、传播情况及其临床影响。NDM的演变凸显了在管理抗菌药物耐药性方面持续存在的挑战以及警惕的分子监测的至关重要性。它还突出了发现新抗生素以对抗耐药细菌的迫切需求。

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