Metagenome analysis of polymicrobial diseases and its application to clinical fields

乳头瘤性指状皮炎(PDD)是由多种细菌包括不可培养的细菌引起的一种新的感染性疾病，是一种多菌疾病。在这个项目中，我们开发了一种适用于PDD元基因组分析的DNA提取方案和基因组序列组装器。通过使用它们，我们获得了高质量的参考元基因组序列，可以用于重建PDD的主要致病因子的基因组。对于唯一可培养的与PDD相关的物种--噬血密螺旋体，我们测定了1个PDD来源的菌株和1个人来源的标准菌株的全基因组序列，另外还测定了5个PDD来源的菌株的高质量草稿序列。通过对这些基因组的比较，我们揭示了这种微生物独特的进化和多样化机制，这些机制包括IS和蠕形螨分子的爆炸性扩增，多个噬菌体感染，以及这些可移动的遗传元件介导的广泛的基因组重排。

Papillomatous digital dermatitis (PDD) is caused by multiple bacteria including non-cultivable species, and is one of the polymicrobial diseases, a new category of infectious diseases. In this project, we developed a protocol for DNA extraction and a genome sequence assembler, both suitable for metagenome analysis of PDD. By using them, we obtained high quality reference metagenome sequences that can be used to reconstitute the genomes of major causative agents of PDD. As for Treponema phagedenis, a uniquely cultivable PDD-related species, we determined the complete genome sequences of one PDD-derived strain and one human-derived standard strain and, in addition, the high quality draft sequences of 5 PDD-derived strains. By comparing these genomes, we revealed unique mechanisms of evolution and diversification of this microbe via explosive amplification of IS and MITE elements, multiple phage infections, and extensive genome rearrangements mediated by these mobile genetic elements.