Domestication and characterization of TM7-the most elusive oral phylum

描述（由申请人提供）：人类微生物组项目提供了与人体相关的微生物的全面清单。下一个挑战是了解它们在人类健康和疾病中的作用，这需要培养感兴趣的物种。与此应用相关，超过一半的口腔微生物被归类为未培养的类群，包括许多与口腔微生物发病机制相关的类群。其中，候选分支TM7门的成员是口腔中最神秘的细菌群。尽管它们普遍存在于人体部位和其他环境中，但尚未有TM7代表被培养为纯培养物。作为一门含有与炎症性粘膜疾病，特别是牙周炎相关的疑似病原体的门，TM7的培养和研究其致病特征的能力已成为微生物学领域的“圣杯”。利用一种新的培养基和富集技术，我们能够将含有TM7的培养物从一个复杂的群落减少到含有与疾病相关的TM7种型（TM7x）的双种共培养物，并与小苗托波菌或非典型微孔菌作为伴侣菌株。我们推测TM7x的生长需要特定的伴侣物种，了解它们之间的关系可能是分离TM7x纯培养的关键。此外，目前TM7x的半纯培养物和本研究可能获得的TM7x纯培养物将使我们能够研究TM7x的基因组学、相互作用组学和致病潜力。本申请旨在通过对TM7x及其伴侣种之间的关系进行详细的分子分析，改进培养纯TM7x的培养基，探索其致病潜力，从而验证我们的假设，实现上述目标。该研究的直接影响是发现了TM7x的培养条件和相关的生物/生理功能。该研究的长期意义在于为许多其他尚未培养的潜在致病物种的培养创造了新的途径。

DESCRIPTION (provided by applicant): The human microbiome project has provided a comprehensive inventory of the microorganisms associated with the human body. The next challenge is to understand their role in human health and disease which requires cultivation of the species of interest. Relevant to this application, more than half of the oral microorganisms are categorized as uncultivated phylotypes including many associated with oral microbial pathogenesis. Among them, members of the candidate division TM7 phylum are the most enigmatic bacterial group in the oral cavity. Despite their ubiquitous occurrence in human body sites and other environments, no TM7 representative has been cultivated as pure culture. As a phylum containing suspected pathogens associated with inflammatory mucosal diseases, particularly periodontitis, cultivation of TM7 and the ability to investigate their pathogenic features has become like a "Holy Grail" in microbiology. Using a novel medium and enrichment techniques, we were able to reduce TM7-containing cultures from a complex community to dual-species co-cultures containing the disease associated TM7 phylotype (TM7x) together with Atopobium parvulum or Veillonella atypica as partner strain. We hypothesize that the growth of TM7x requires specific partner species and that understanding their relationship may be the key for isolating pure culture of TM7x. Furthermore, the present semi-pure cultures of TM7x and the possible pure TM7x cultures obtained through this study will enable our ability to study genomics, interactomics and the pathogenic potential of TM7x. This application aims to test our hypothesis and achieve these goals through detailed molecular analyses of the relationship between TM7x and its partner species, improving the medium for cultivating pure TM7x, as well as exploring its pathogenic potential. The immediate impact of the study is the discovery of cultivation conditions for TM7x and the associated biological/physiological functions. The long-term significance of the study is the creation of a new pathway for cultivation of many other yet-to-be cultured potentially pathogenic species.