Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety and Beijing Laboratory for Food Quality and Safety, Beijing, China.
mBio. 2018 Jul 3;9(4):e00943-18. doi: 10.1128/mBio.00943-18.
The recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route of among species in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis of isolates collected in a hospital in Hangzhou, China. We found that -carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread of The gene was found on either chromosomes or plasmids, but in most of the isolates, was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission of and the coexistence of with other genes encoding β-lactamases and fluoroquinolone resistance in the isolates. These findings indicate that is heterogeneously disseminated in both commensal and pathogenic strains of , suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology of among hospital-associated strains. Colistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergent colistin resistance gene threatens the clinical utility of colistin and has gained global attention. How spreads in hospital settings remains unknown and was investigated by whole-genome sequencing of -carrying in this study. The findings revealed extraordinary flexibility of in its spread among genetically diverse hosts and plasmids, nosocomial transmission of -carrying , and the continuous emergence of novel Inc types of plasmids carrying and new variants. Additionally, was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology of and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.
最近出现的一种可转移的多粘菌素耐药机制 MCR-1 引起了全球的关注，因为它对治疗多重耐药革兰氏阴性菌引起的感染的临床治疗构成了威胁。然而，在临床环境中，种间传播的可能途径在很大程度上尚不清楚。在这里，我们对中国杭州一家医院采集的 分离株进行了全面的基因组分析。我们发现，来自临床感染和住院患者及健康志愿者粪便的携带 基因的分离株在遗传上是多样化的，并且在系统发育上没有密切相关，这表明克隆扩张并不是 的传播途径。该基因位于染色体或质粒上，但在大多数 分离株中， 位于质粒上。质粒的遗传结构显示出相当大的多样性，这表现在不同功能的插入序列（IS）元件、毒素-抗毒素（TA）系统、重金属抗性决定因素和广泛宿主范围质粒的 Rep 蛋白上。此外，基因组分析显示 在医院环境中的传播以及 与其他编码β-内酰胺酶和氟喹诺酮耐药的基因在 分离株中的共存。这些发现表明， 是在 的共生和病原菌株中不均匀传播的，表明该基因在与宿主的不同遗传背景相关联方面具有很高的灵活性，并为医院相关 菌株中 的基因组流行病学提供了新的见解。多粘菌素是治疗广泛耐药革兰氏阴性菌引起的感染的为数不多的有效药物之一。最近出现的 多粘菌素耐药基因威胁到多粘菌素的临床应用，并引起了全球的关注。 在医院环境中是如何传播的仍然未知，本研究通过对携带 基因的 进行全基因组测序进行了调查。研究结果表明， 在遗传上多样化的 宿主和质粒中具有非凡的传播灵活性，携带 的质粒在医院内传播，以及新型携带 的 Inc 型质粒和新的 变体不断出现。此外，还发现 基因经常与其他编码β-内酰胺类和氟喹诺酮类耐药的基因相关联。这些发现为 的传播和流行病学提供了重要信息，对公共卫生具有重要意义，因为这些信息有望有助于控制这一重大抗生素耐药性威胁。
