Metagenome analysis of polymicrobial diseases and its application to clinical fields

指乳头状瘤性皮炎（Papillomatous digital dermatitis，PDD）是由多种细菌（包括非可培养菌）引起的一种多菌性疾病，是一类新的传染病。在这个项目中，我们开发了一个协议，DNA提取和基因组序列组装，都适合PDD宏基因组分析。通过使用它们，我们获得了高质量的参考宏基因组序列，可用于重建PDD的主要致病因子的基因组。对于噬菌密螺旋体，一种独特的可培养的PDD相关物种，我们确定了一种PDD衍生菌株和一种人源标准菌株的全基因组序列，此外，还确定了5种PDD衍生菌株的高质量草图序列。通过比较这些基因组，我们揭示了独特的进化和多样化的机制，这种微生物通过爆炸性扩增的IS和MITE元素，多个噬菌体感染，和广泛的基因组重排介导的这些移动的遗传元件。

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.