Discovery of mcr-1-Mediated Colistin Resistance in a Highly Virulent Escherichia coli Lineage.
Discovery of mcr-1-Mediated Colistin Resistance in a Highly Virulent Escherichia coli Lineage.
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DOI：
10.1128/msphere.00486-18
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发表时间：
2018-10-10
期刊：
影响因子：
4.8
通讯作者：
Beatson SA
中科院分区：
文献类型：
--
作者：
Forde BM;Zowawi HM;Harris PNA;Roberts L;Ibrahim E;Shaikh N;Deshmukh A;Sid Ahmed MA;Al Maslamani M;Cottrell K;Trembizki E;Sundac L;Yu HH;Li J;Schembri MA;Whiley DM;Paterson DL;Beatson SA
大肠杆菌ST 95是一种全球性传播的克隆，经常与血流感染和新生儿脑膜炎有关。然而，ST 95谱系是由临床分离株中低水平的耐药性定义的，这通常提供了简单的治疗选择。在这里，我们提供了第一个详细的基因组分析E。coli ST 95分离株具有高毒力潜力和对多种抗生素的抗性。利用该基因组，我们预测了其毒力和抗生素耐药机制，包括质粒携带的mcr-1基因介导的对最后一线抗生素的耐药性。发现一种对几乎所有抗生素都具有耐药性且具有高毒力潜力的ST 95分离株具有重要的临床意义，并强调了监测这一重要全球谱系中抗生素耐药性发展的新趋势和新兴趋势的必要性。由质粒携带的移动的粘菌素耐药基因（mcr-1）介导的对最后一线多粘菌素的耐药性代表了对全球人类健康的新威胁。在此，我们提供了mcr-1阳性多重耐药大肠埃希菌菌株（MS8345）的完整基因组序列。我们发现MS 8345属于血清型O2：K1：H4，具有一个大的241，164-bp的IncHI 2质粒，该质粒携带15个其他抗生素耐药基因（包括超广谱β-内酰胺酶blaCTX-M-1）和3个假定的多药外排系统，并含有14个染色体编码的抗生素耐药基因。MS8345还携带一个大的ColV样毒力质粒，该质粒与E.大肠杆菌菌血症。全基因组同源性分析表明，MS8345在序列类型95（ST 95）谱系中的一个离散进化枝内聚类，并且MS8345与与新生儿脑膜炎相关的高毒力O45：K1：H4克隆非常密切相关。总的来说，在这种毒力大肠杆菌中获得携带对粘菌素和多种其他抗生素的抗性的质粒。大肠杆菌谱系是令人担忧的，并可能预示着一个时代，其中ST95感染的经验性治疗变得越来越困难。重要性大肠杆菌ST 95是一种全球传播的克隆，经常与血流感染和新生儿脑膜炎有关。然而，ST 95谱系是由临床分离株中低水平的耐药性定义的，这通常提供了简单的治疗选择。在这里，我们提供了第一个详细的基因组分析E。coli ST 95分离株具有高毒力潜力和对多种抗生素的抗性。利用该基因组，我们预测了其毒力和抗生素耐药机制，包括质粒携带的mcr-1基因介导的对最后一线抗生素的耐药性。发现一种对几乎所有抗生素都具有耐药性且具有高毒力潜力的ST 95分离株具有重要的临床意义，并强调了监测这一重要全球谱系中抗生素耐药性发展的新趋势和新兴趋势的必要性。
Escherichia coli ST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of an E. coli ST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-borne mcr-1 gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage. Resistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene (mcr-1) represents a new threat to global human health. Here we present the complete genome sequence of an mcr-1-positive multidrug-resistant Escherichia coli strain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamase blaCTX-M-1) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated with E. coli bacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulent E. coli lineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult. IMPORTANCE Escherichia coli ST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of an E. coli ST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-borne mcr-1 gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.