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。与这一应用相关的是，超过一半的口腔微生物被归类为未培养的系统型，其中许多与口腔微生物的发病机制有关。其中，候选科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代表作为纯培养物培养出来。作为一门含有与炎症性黏膜疾病，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性的能力已成为微生物学中的一个圣杯。使用一种新的培养基和增菌技术，我们能够将含有TM7的培养物从一个复杂的群落减少到双物种共培养，其中包含与疾病相关的TM7系统型(TM7x)，以及作为配对菌株的微小阿托卜菌或非典型韦洛氏菌。我们推测，TM7x的生长需要特定的配对物种，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的半纯培养和通过本研究获得的可能的纯TM7x培养将使我们有能力研究TM7x的基因组学、相互作用和致病潜力。这项应用旨在通过对TM7x与其配对物种之间关系的详细分子分析，改进培养纯TM7x的介质，以及探索其致病潜力，来验证我们的假设并实现这些目标。这项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。这项研究的长期意义是为培育许多其他尚未培养的潜在致病物种开辟了一条新的途径。

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.