摘要

由于质粒介导的多粘菌素抗性基因mcr-1首次在中国大肠杆菌和肺炎克雷伯菌中报道，全世界只有一种mcr-1阳性的志贺氏痢疾杆菌分离株含有失活的mcr-1。在这里，我们筛选了2003年至2015年在中国分离的1650株历史悠久的S. sonnei菌株的mcr-1。我们确定了mcr-1阳性分离株的抗菌药物敏感性和耐药基因，并通过质粒共轭研究了多粘菌素耐药性的转移性。使用脉冲场凝胶电泳，质粒谱和Southern印迹分析遗传关系和质粒特征，并对mcr-1阳性质粒进行测序。总之，我们从上海（2010-2012）发现了6个mcr-1阳性的S. sonnei菌株，其具有多粘菌素B抗性（MIC 4-8μg/ mL）。其中四种表现出对多种药物耐药性（MDR），包括对阿奇霉素和第三代头孢菌素的耐药性，以及在不同质粒上共同携带blaCTX-M-14，mph（A）和blaTEM。尽管观察到一些差异，包括各种和丰富的插入序列/模式（IS1294，IS1和ISApl1）以及不同的重组抗体区域，但Mcr-1阳性质粒具有与参考质粒相似的高度相似的IncI2主链。 S. sonnei的Mcr-1可追溯至2006年中期。我们首次报道了MDR S. sonnei在中国的活性mcr-1的存在情况，该数据自至少2010年以来一直存在。我们的研究突出了mcr-1携带质粒上的多种活动性遗传元件，可能导致高肠杆菌科中mcr-1水平转移率。我们的研究结果强调持续国家和国际对mcr-1阳性志贺氏菌的监测和抗生素耐药模式变化的重要性。

Since the plasmid-mediated polymyxin resistance gene mcr-1 was first reported inEscherichia coli and Klebsiella pneumoniae in China, only one mcr-1-positive isolate ofShigella sonnei, containing inactivated mcr-1, has been reported worldwide. Here, we screened 1650 historical S. sonnei strains isolated from 2003 to 2015 in China for mcr-1. We determined the antimicrobial susceptibilities and resistance genes of mcr-1-positive isolates and investigated the transferability of polymyxin resistance by plasmid conjugation. Pulsed-field gel electrophoresis, plasmid profiles, and Southern blot were used to analyze genetic relationships and plasmid characteristics, and mcr-1-positive plasmids were sequenced. In total, we identified six mcr-1-positive S. sonnei isolates from Shanghai (2010–2012) with polymyxin B resistance (MIC 4–8 μg/mL). Four of these exhibited multidrug resistance (MDR), including resistance to azithromycin and third-generation cephalosporins, and co-harbored blaCTX-M-14, mph (A), and blaTEM on different plasmids. Mcr-1-positive plasmids shared highly similar IncI2 backbones that resembled reference plasmids, although some differences were observed, including various and abundant insertion sequences/patterns (IS1294, IS1, and ISApl1) and a diverse recombination shufflon region. Mcr-1 in S. sonnei may date back to mid-2006. For the first time, we report the presence of active mcr-1 in MDR S. sonnei in China, which has existed since at least 2010. Our study highlights the diverse mobile genetic elements on mcr-1-harboring plasmids, potentially resulting in high rates of mcr-1 horizontal transfer among Enterobacteriaceae. Our findings emphasize the importance of continuous national and international surveillance of mcr-1-positive Shigella and changes in antibiotic resistance patterns.

https://www.sciencedirect.com/science/article/pii/S0924857918300578