Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram-negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene (mcr-1) is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-1-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-1-positive Escherichia coli (E15004, E15015 and E15017) and define general features through analyses of bacterial comparative genomics. Further genomic mining together with sequence typing allowed us to elucidate that the MCR-1-carrying E. coli E15017 belongs to the sequence type ST648 and coproduces extended-spectrum β-lactamase (ESBL). Given the fact that ST648 has been known to associate with either New Delhi metallo-β-lactamase 1 or ESBL, our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.
通常认为多粘菌素是抵御多药耐受的革兰阴性病原菌严重感染的最后一道防线。 最新研究表明在动物类食品和人体肠道菌群中存在一种多粘菌素抗性基因 (mcr-1)。这一惊人发现对上述传统观点提出了严重挑战。更为惊讶的是, 该 mcr-1 基因可与其他抗生素抗性基因共存, 极大增加了产生具有广泛耐药的超级 细菌的可能性。但是, 关于mcr-1 阳性细菌的基因组学特征鲜见报道。本研究对 3 株 mcr-1 阳性人源大肠杆菌(E15004, E15015 和E15017)开展了全基因组 测序, 并通过比较基因组学描述了其基因组学特征。基因组深入挖掘和序列分型 实验揭示了序列型为ST648 的大肠杆菌E15017 不仅编码MCR-1 多粘菌素耐药 基因, 而且携带超广谱β-内酰胺耐药基因(ESBL)。鉴于序列型ST648 的大肠杆 菌通常与新德里β-内酰胺耐药-1 (NDM-1) 或ESBL 紧密关联这一事实, 我们的 研究结果提示了具有MCR-1 和ESBL 耐药的ST648 细菌发展成流行性克隆的潜 在风险。.
Keywords: Colistin resistance; Extended-spectrum beta-lactam (ESBL); MCR-1; ST648.