Data_Sheet_1_Characterization of a NDM-1- Encoding Plasmid pHFK418-NDM From a Clinical Proteus mirabilis Isolate Harboring Two Novel Transposons, Tn6624 and Tn6625.docx

Acquisition of the blaNDM–1 gene by Proteus mirabilis is a concern because it already has intrinsic resistance to polymyxin E and tigecycline antibiotics. Here, we describe a P. mirabilis isolate that carries a pPrY2001-like plasmid (pHFK418-NDM) containing a blaNDM–1 gene. The pPrY2001-like plasmid, pHFK418-NDM, was first reported in China. The pHFK418-NDM plasmid was sequenced using a hybrid approach based on Illumina and MinION platforms. The sequence of pHFK418-NDM was compared with those of the six other pPrY2001-like plasmids deposited in GenBank. We found that the multidrug-resistance encoding region of pHFK418-NDM contains ΔTn10 and a novel transposon Tn6625. Tn6625 consists of ΔTn1696, Tn6260, In251, ΔTn125 (carrying blaNDM–1), ΔTn2670, and a novel mph(E)-harboring transposon Tn6624. In251 was first identified in a clinical isolate, suggesting that it has been transferred efficiently from environmental organisms to clinical isolates. Genomic comparisons of all these pPrY2001-like plasmids showed that their relatively conserved backbones could integrate the numerous and various accessory modules carrying multifarious antibiotic resistance genes. Our results provide a greater depth of insight into the horizontal transfer of resistance genes and add interpretive value to the genomic diversity and evolution of pPrY2001-like plasmids.

奇异变形杆菌（Proteus mirabilis）获得blaNDM–1基因（blaNDM–1 gene）是一项值得关注的公共卫生事件，因其本身已对多粘菌素E（polymyxin E）与替加环素（tigecycline）两类抗生素存在固有耐药性。本研究报道一株携带pPrY2001型类质粒（pPrY2001-like plasmid，命名为pHFK418-NDM）且携带有blaNDM–1基因的奇异变形杆菌临床分离株。该pHFK418-NDM质粒为国内首次报道的pPrY2001型类质粒。
本研究采用基于Illumina与MinION测序平台的混合测序策略对pHFK418-NDM质粒进行全基因组测序，并将其序列与GenBank中已提交的其余6株pPrY2001型类质粒进行比对分析。结果显示，pHFK418-NDM的多重耐药编码区包含缺失型转座子ΔTn10与新型转座子Tn6625。Tn6625由缺失型转座子ΔTn1696、Tn6260、In251、携带blaNDM–1基因的缺失型转座子ΔTn125、缺失型转座子ΔTn2670以及新型携带mph(E)的转座子Tn6624构成。其中In251首次于临床分离株中被鉴定，提示其可从环境微生物高效转移至临床分离菌株。
对所有pPrY2001型类质粒的基因组比较分析表明，其相对保守的骨架结构可整合携带多样抗生素耐药基因的各类附属模块。本研究结果为耐药基因的水平转移机制提供了更深入的认知，并为解析pPrY2001型类质粒的基因组多样性与演化历程增添了重要的参考价值。