IS26 Is Responsible for the Evolution and Transmission of bla(NDM)-Harboring Plasmids in Escherichia coli of Poultry Origin in China.
IS26 Is Responsible for the Evolution and Transmission of bla(NDM)-Harboring Plasmids in Escherichia coli of Poultry Origin in China.
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DOI：
10.1128/msystems.00646-21
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发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Jiang HX
中科院分区：
文献类型：
--
作者：
Zhao QY;Zhu JH;Cai RM;Zheng XR;Zhang LJ;Chang MX;Lu YW;Fang LX;Sun J;Jiang HX
碳青霉烯类耐药肠杆菌科细菌是导致医院感染的最重要病原体之一，其治疗可能具有挑战性。由产新德里金属-β-内酰胺酶（NDM）的大肠埃希菌分离株表达的blaNDM碳青霉烯酶基因已在全球范围内的人类、环境样本和多种其他来源中发现。重要的是，这些基因也在农场动物中发现，这些动物被认为是NDM的储存库和人类感染的重要来源。然而，尚未直接观察到blaNDM遗传背景和携带blaNDM的质粒的动态进化，因此难以评估blaNDM基因水平传播的程度。在这项研究中，我们检测了NDM-1（n = 1），NDM-5（n = 24）和NDM-9（n = 8）的变异表达的E。2016年至2017年从中国家禽中分离的大肠杆菌菌株。通过分析blaNDM基因的直接遗传环境，我们发现IS26与多种类型的blaNDM多药耐药区域相关，并且我们鉴定了各种IS26衍生的环状中间体。重要的是，在E. coli菌株GD33中，我们推测当存在IS26时，IncHI 2和IncI 1质粒可以融合。我们对blaNDM侧翼的IS26元件的分析使我们能够提出IS26元件在多药耐药区（MRR）的演变和blaNDM的传播中的重要作用。据我们所知，这是blaNDM遗传背景和blaNDM携带质粒的动态进化的第一个描述。这些发现可能有助于主动限制这些产NDM分离株从食用动物传播给人类。重要性肠杆菌目成员的碳青霉烯耐药性是一个日益严重的公共卫生问题，与发展中国家和工业化国家的高死亡率有关。不仅如此，在兽药领域，近年来动物尤其是食用动物中出现产新德里金属β-内酰胺酶大肠埃希菌分离株的问题日益受到关注。blaNDM的广泛传播与移动的遗传元件（MGE）和质粒密切相关。虽然以前的分析已经探讨了许多不同的MGE与blaNDM动员的关联，但对E.杆菌在这里，我们报告了IS26在形成多种类型的blaNDM多药耐药盒和携带blaNDM的质粒的动态重组中的重要作用。这些结果表明，应重视监测携带blaNDM质粒在大肠杆菌中的传播和进一步进化。来源于食用动物的大肠杆菌菌株。
Carbapenem-resistant Enterobacteriaceae are some of the most important pathogens responsible for nosocomial infections, which can be challenging to treat. The blaNDM carbapenemase genes, which are expressed by New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli isolates, have been found in humans, environmental samples, and multiple other sources worldwide. Importantly, these genes have also been found in farm animals, which are considered an NDM reservoir and an important source of human infections. However, the dynamic evolution of blaNDM genetic contexts and blaNDM-harboring plasmids has not been directly observed, making it difficult to assess the extent of horizontal dissemination of the blaNDM gene. In this study, we detected NDM-1 (n = 1), NDM-5 (n = 24), and NDM-9 (n = 8) variants expressed by E. coli strains isolated from poultry in China from 2016 to 2017. By analyzing the immediate genetic environment of the blaNDM genes, we found that IS26 was associated with multiple types of blaNDM multidrug resistance regions, and we identified various IS26-derived circular intermediates. Importantly, in E. coli strain GD33, we propose that IncHI2 and IncI1 plasmids can fuse when IS26 is present. Our analysis of the IS26 elements flanking blaNDM allowed us to propose an important role for IS26 elements in the evolution of multidrug-resistant regions (MRRs) and in the dissemination of blaNDM. To the best of our knowledge, this is the first description of the dynamic evolution of blaNDM genetic contexts and blaNDM-harboring plasmids. These findings could help proactively limit the transmission of these NDM-producing isolates from food animals to humans. IMPORTANCE Carbapenem resistance in members of the order Enterobacterales is a growing public health problem that is associated with high mortality in developing and industrialized countries. Moreover, in the field of veterinary medicine, the occurrence of New Delhi metallo-β-lactamase-producing Escherichia coli isolates in animals, especially food-producing animals, has become a growing concern in recent years. The wide dissemination of blaNDM is closely related to mobile genetic elements (MGEs) and plasmids. Although previous analyses have explored the association of many different MGEs with mobilization of blaNDM, little is known about the evolution of various genetic contexts of blaNDM in E. coli. Here, we report the important role of IS26 in forming multiple types of blaNDM multidrug resistance cassettes and the dynamic recombination of plasmids bearing blaNDM. These results suggest that significant attention should be paid to monitoring the transmission and further evolution of blaNDM-harboring plasmids among E. coli strains of food animal origin.