Heterogeneous and Flexible Transmission of mcr-1 in Hospital-Associated Escherichia coli.
Heterogeneous and Flexible Transmission of mcr-1 in Hospital-Associated Escherichia coli.
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mcr-1 在医院相关大肠杆菌中的异质和灵活传播
DOI：
10.1128/mbio.00943-18
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发表时间：
2018-07-03
期刊：
影响因子：
6.4
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Shen Y;Wu Z;Wang Y;Zhang R;Zhou HW;Wang S;Lei L;Li M;Cai J;Tyrrell J;Tian GB;Wu C;Zhang Q;Shen J;Walsh TR;Shen Z
摘要最近出现的一种可转移的粘菌素耐药机制，MCR-1，由于其对多重耐药革兰氏阴性菌引起的感染的临床治疗的威胁而引起了全球的关注。然而，临床环境中肠杆菌科菌种中mcr-1的可能传播途径在很大程度上尚不清楚。在这里，我们提出了一个全面的基因组分析大肠杆菌分离株收集在杭州，中国医院。我们发现，临床感染和住院患者及健康志愿者粪便中携带mcr-1的分离株具有遗传多样性，且在遗传学上不密切相关，表明克隆扩增与mcr-1的传播无关。mcr-1基因存在于染色体或质粒上，但在大多数大肠杆菌中，mcr-1基因的表达与大肠杆菌中的mcr-1基因的表达无关。大肠杆菌分离株，mcr-1携带在质粒上。质粒的遗传背景显示出相当大的多样性，证明了不同的功能插入序列（IS）元素，毒素-抗毒素（TA）系统，重金属抗性决定簇，和广泛的主机范围质粒的Rep蛋白。此外，基因组分析显示mcr-1在大肠埃希菌中存在院内传播，mcr-1与其他编码β-内酰胺酶和氟喹诺酮耐药的基因共存。大肠杆菌分离株。这些结果表明，mcr-1在大肠杆菌的致病性和非致病性菌株中均为异质性播散。大肠杆菌中，表明该基因与宿主不同的遗传背景相关，具有高度灵活性，并为医院相关大肠杆菌中mcr-1的基因组流行病学提供了新的见解。大肠杆菌菌株。重要性粘菌素是治疗广泛多重耐药革兰氏阴性菌引起的感染的极少数可用药物之一。最近出现的mcr-1粘菌素耐药基因威胁着粘菌素的临床应用，并已引起全球关注。mcr-1如何在医院环境中传播尚不清楚，本研究通过对携带mcr-1的大肠埃希菌进行全基因组测序进行了研究。这些发现揭示了mcr-1在遗传多样性E.大肠杆菌宿主和质粒，携带mcr-1的大肠杆菌的医院传播。大肠杆菌中，以及携带mcr-1和新mcr-1变体的新型Inc型质粒的不断出现。此外，发现mcr-1通常与编码β-内酰胺类和氟喹诺酮类耐药的其他基因相关。这些发现提供了有关mcr-1传播和流行病学的重要信息，具有重要的公共卫生意义，因为这些信息有望促进控制这一重大抗生素耐药性威胁。重要性粘菌素是治疗广泛多重耐药革兰氏阴性菌引起的感染的极少数可用药物之一。最近出现的mcr-1粘菌素耐药基因威胁着粘菌素的临床应用，并已引起全球关注。mcr-1如何在医院环境中传播尚不清楚，本研究通过对携带mcr-1的大肠埃希菌进行全基因组测序进行了研究。这些发现揭示了mcr-1在遗传多样性E.大肠杆菌宿主和质粒，携带mcr-1的大肠杆菌的医院传播。大肠杆菌中，以及携带mcr-1和新mcr-1变体的新型Inc型质粒的不断出现。此外，发现mcr-1通常与编码β-内酰胺类和氟喹诺酮类耐药的其他基因相关。这些发现提供了有关mcr-1传播和流行病学的重要信息，具有重要的公共卫生意义，因为这些信息有望促进控制这一重大抗生素耐药性威胁。
ABSTRACT 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 mcr-1 among Enterobacteriaceae species in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis of Escherichia coli isolates collected in a hospital in Hangzhou, China. We found that mcr-1-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 mcr-1. The mcr-1 gene was found on either chromosomes or plasmids, but in most of the E. coli isolates, mcr-1 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 mcr-1 and the coexistence of mcr-1 with other genes encoding β-lactamases and fluoroquinolone resistance in the E. coli isolates. These findings indicate that mcr-1 is heterogeneously disseminated in both commensal and pathogenic strains of E. coli, 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 mcr-1 among hospital-associated E. coli strains. IMPORTANCE Colistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergent mcr-1 colistin resistance gene threatens the clinical utility of colistin and has gained global attention. How mcr-1 spreads in hospital settings remains unknown and was investigated by whole-genome sequencing of mcr-1-carrying Escherichia coli in this study. The findings revealed extraordinary flexibility of mcr-1 in its spread among genetically diverse E. coli hosts and plasmids, nosocomial transmission of mcr-1-carrying E. coli, and the continuous emergence of novel Inc types of plasmids carrying mcr-1 and new mcr-1 variants. Additionally, mcr-1 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 mcr-1 and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat. IMPORTANCE Colistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergent mcr-1 colistin resistance gene threatens the clinical utility of colistin and has gained global attention. How mcr-1 spreads in hospital settings remains unknown and was investigated by whole-genome sequencing of mcr-1-carrying Escherichia coli in this study. The findings revealed extraordinary flexibility of mcr-1 in its spread among genetically diverse E. coli hosts and plasmids, nosocomial transmission of mcr-1-carrying E. coli, and the continuous emergence of novel Inc types of plasmids carrying mcr-1 and new mcr-1 variants. Additionally, mcr-1 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 mcr-1 and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.