| 论文题目: | Dissemination and Mechanism for the MCR-1 Colistin Resistance |
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| 作者: | Gao, Rongsui Hu, Yongfei Li, Zhencui Sun, Jian Wang, Qingjing Lin, Jingxia Ye, Huiyan Liu, Fei Srinivas, Swaminath Li, Defeng Zhu, Baoli Liu, Ya-Hong Tian, Guo-Bao Feng, Youjun |
| 联系作者: | Feng, Youjun*(Zhu Baoli) |
| 刊物名称: | PLoS Pathog |
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| 年份: | 2016 |
| 影响因子: | 7.758 |
| 论文下载: | http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005957 |
| 摘要: | Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance. |
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