Environmental Uncultivable Bacteria Model for Understanding Human Periodontitis

描述（由申请人提供）：据估计，人体内的细菌细胞比人体细胞多10倍；这些细菌中有许多尚未被培养。从历史上看，可培养细菌在人类发展、健康和疾病方面发挥了重要作用。我们有理由推测，未培养的细菌群（占人类肠道的近80%和人类口腔微生物群的68%）参与了类似的功能。TM7是细菌的众多候选分支之一，完全由未培养的成员组成，并且与人体（皮肤、口腔、肠道和阴道液）有关。最近发现TM7与人类口腔疾病有关。今年，作为我们第一个SC3资助周期的一部分，基于16S核糖体DNA基因（16S rDNA）序列分析，我们确定并发表了TM7细菌的环境来源，该细菌与人类相关的口腔TM7具有bbbb99 %的同源性（Dinis et al. 2011）。令人惊讶的是，我们的环境TM7细菌与人类口腔相关TM7的序列同源性高于人体其他地方发现的大多数TM7细菌，并且比人类口腔中的TM7丰富多达五倍。我们假设环境TM7细菌可以作为理解人类疾病的模式生物。在这个更新申请中，我们建议对我们样本中的环境TM7模式生物的全基因组进行测序和注释。基因组序列可以帮助我们预测基因对这种潜在新出现的人类病原体的致病性、代谢途径、营养需求、运动能力和其他生物学特性的假定功能。

DESCRIPTION (provided by applicant): It has been estimated that the human body harbors 10 times more bacterial cells than human cells; many of those bacteria are yet uncultured. Historically, cultivable bacteria have been instrumental in human development, health, and diseases. It is reasonable to speculate that uncultured bacterial groups, which comprise nearly 80% of the human gut and 68% of the human oral microbial consortia, participate in similar functions. TM7, one of many candidate divisions of Bacteria, is comprised entirely of uncultured members, and has been associated with the human body (skin, mouth, gut, and vaginal fluid). Recently TM7 were associated with human oral diseases. This year, as part of our first SC3 funding cycle, we identified and published an environmental source for a TM7 bacterium with >99% identity to a human-associated oral TM7, based on 16S ribosomal DNA gene (16S rDNA) sequence analysis (Dinis et al. 2011). Surprisingly, our environmental TM7 bacterium has higher sequence homology to the human oral-associated TM7 than most other TM7 bacteria found elsewhere in the human body and up to five times more abundant than TM7 in the human oral cavity. We hypothesize that environmental TM7 bacteria can serve as a model organism for understanding human diseases. In this renewal application, we propose to sequence and annotate the whole genome of the environmental TM7 model organism in our samples. A genome sequence can help us make predictions for putative function of genes to pathogenicity, metabolic pathways, nutrient requirements, motility capabilities, and other biological attributes o this potential emerging human pathogen. PUBLIC HEALTH RELEVANCE: This project seeks to establish a model of the emerging and uncultured bacterium TM7, which has been associated with human oral diseases, to better understand the role TM7 plays in human health. Our past publications proposed that an environmental TM7 with over 99% identity to a human-associated TM7 could serve as that model organism in the study of pathogenic genes using metagenomics and circumvent problems related to intrusive methods when collecting samples from humans.