The Birth and Demise of the ISApl1-mcr-1-ISApl1 Composite Transposon: the Vehicle for Transferable Colistin Resistance.
The Birth and Demise of the ISApl1-mcr-1-ISApl1 Composite Transposon: the Vehicle for Transferable Colistin Resistance.
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DOI：
10.1128/mbio.02381-17
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发表时间：
2018-02-13
期刊：
影响因子：
6.4
通讯作者：
Chandler M
中科院分区：
文献类型：
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作者：
Snesrud E;McGann P;Chandler M
含有移动的粘菌素耐药基因mcr-1的~ 2，609-bp DNA片段的来源和移动仍然是不确定性的来源，但最近的证据表明该基因起源于莫拉氏菌属。此外，mcr-1可以作为ISApl 1侧翼的复合转座子（Tn 6330）移动，但许多序列已被鉴定为不含ISApl 1或仅含单拷贝（单端）。为了进一步阐明mcr-1的起源和动员，我们使用Geneious R8软件套件全面分析了截至本文撰写时（2017年9月）存在和不存在相关ISApl 1的GenBank中每个完整mcr-1结构的遗传环境（n = 273）。这表明，2，609 bp mcr-1结构可能来自一种新的莫拉氏菌属种的近亲，该种新的莫拉氏菌属种含有与典型序列具有>96%核苷酸同一性的染色体区域。该染色体区域以AT和CG二核苷酸为界，AT和CG二核苷酸已经在迄今为止描述的所有完整Tn 6330的内端（IE）上描述，并且代表由ISApl 1转座产生的祖先2-bp靶位点重复（TSD）。我们进一步证明，所有只有一个ISApl 1拷贝或没有ISApl 1拷贝的mcr-1结构都是通过从祖先Tn 6330中删除ISApl 1形成的，可能是通过与“拷贝-输出-粘贴-输入”转座机制相关的过程。最后，我们表明，只有罕见的单端结构的例子，保留了一部分切除下游ISApl 1，包括整个反向右重复可能是能够动员。对GenBank中所有完整mcr-1序列进行综合分析，以鉴定一种新型莫拉菌属染色体上与典型mcr-1结构具有显著同源性的区域，该区域可能代表该重要基因的起源。这些数据还表明，所有缺乏一个或两个侧翼ISApl 1的mcr-1结构都是由祖先复合转座子形成的，这些转座子随后通过失败的转座过程失去了插入序列。这一观察结果最终表明，mcr-1的动员作为复合转座子的一部分发生，缺乏下游ISApl 1的结构不能动员。
The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked composite transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization. A comprehensive analysis of all intact mcr-1 sequences in GenBank was used to identify a region on the chromosome of a novel Moraxella species with remarkable homology to the canonical mcr-1 structure and that likely represents the origin of this important gene. These data also demonstrate that all mcr-1 structures lacking one or both flanking ISApl1 were formed from ancestral composite transposons that subsequently lost the insertion sequences by a process of abortive transposition. This observation conclusively shows that mobilization of mcr-1 occurs as part of a composite transposon and that structures lacking the downstream ISApl1 are not capable of mobilization.