Molecular and pathogenic study of an oral TM7 strain, the first cultivated ultra-small bacterium

项目摘要/摘要 增加我们对人类相关尚未培养的细菌的知识是至关重要的 了解它们在人类疾病中的潜在作用。TM7门就是这样一组细菌。 尽管它无处不在地存在于环境和人体部位以及它的潜力 在牙周炎中的意义，没有可培养的代表TM7门，直到 最近。此外，TM7属于新描述的候选叶霉辐射(CPR)细菌， 它们占整个细菌结构域的15%(&gt；35门)，缺乏分离的代表性。 值得注意的是，CPR生物共享在其他细菌领域中不存在的独特生物学， 这包括但不限于超小细胞尺寸(200-500 nm)和具有 新陈代谢能力高度受限。我们实验室分离到了第一个人类口腔TM7种(TM7x)作为 寄生在其宿主细菌XH001(一种口腔放线菌)表面的专性共生寄生虫 溶牙杆菌品系)。使用TM7x/XH001作为模型系统，本提案试图实现三个目标 基本的知识差距：(1)控制生物多样性的具体分子机制是什么 TM7x与其宿主细菌之间的相互作用？(2)相同的规则和机制是否适用于所有TM7 成员？(3)TM7在人类粘膜炎症性疾病中起什么作用？最终目标是 揭开TM7等CPR细菌的秘密生活方式，真正掌握它们对人类的影响 疾病和环境。 Bor博士在他的博士后研究中一直在研究生理和 TM7x/XH001相互作用的表型行为及其致病机制的研究 TM7细菌是他研究的合乎逻辑的延伸。拟议的K99/R00研究旨在 补充Bor博士以前的研究经验，并在必要的技术和智力方面对他进行培训 成为一名独立调查员的技能。Bor博士将在一项领先的研究中接受培训 加州大学洛杉矶分校的研究所。他的主要导师史博士，以及共同导师何博士、麦克莱恩博士和杜赫斯特博士是 致力于推动牙科研究的成熟、有能力的人。 在K99课程的指导阶段结束后，Bor博士的职业目标是成为一名终身教职员工 在一个领先的学术研究机构，在那里他可以进一步发展他的心肺复苏研究计划 细菌，同时指导和教育学生。Bor博士提出的工作将为以下方面提供关键见解 这种独特的寄主相关细菌的生理学和致病机制，可能有助于 治疗牙周炎的新型治疗工具的开发。

Project Summary/Abstract Increasing our knowledge of the human-associated as-yet-uncultivated bacteria is essential in understanding their potential role in human diseases. The TM7 phylum is one such group of bacteria. Despite its ubiquitous presence in the environment and in human body sites as well as its potential implication in periodontitis, no cultivable representatives of the TM7 phylum have been isolated until very recently. Furthermore, TM7 belongs to the newly described Candidate Phyla Radiation (CPR) bacteria, which comprise >15% (>35 phyla) of the entire bacterial domain and lack an isolated representative. Remarkably, CPR organisms share unique biology that does not exist in the rest of the bacterial domain, which include but not limited to ultra-small cell size (200-500nm) and reduced genome (<1Mb) that has highly restricted metabolic capabilities. Our lab isolated the first human oral TM7 species (TM7x) as an obligate epibiotic parasite that lives on the surface of its host bacterium XH001 (an oral Actinomyces odontolyticus strain). Using TM7x/XH001 as a model system, this proposal seeks to fulfill three fundamental knowledge gaps: (1) What are the specific molecular mechanisms that govern the interaction between TM7x and its host bacteria? (2) Do the same rules and mechanisms apply to all TM7 members? (3) What is the role of TM7 in human mucosal inflammatory diseases? The ultimate goal is to unravel the secret lifestyle of TM7 and other CPR bacteria, and truly grasp their impact on human diseases and the environment. Dr. Bor has spent his postdoctoral research studies characterizing the physiological and phenotypic behaviors of TM7x/XH001 interaction and therefore, mechanistic and pathogenic studies of the TM7 bacteria is a logical extension of his research. The proposed K99/R00 research is designed to supplement Dr. Bor's prior research experiences and to train him in required technical and intellectual skills to become an independent investigator. Dr. Bor will be trained at one of the leading research institutes, UCLA. His primary mentor, Dr. Shi, and co-mentors, Dr. He, Dr. McLean and Dr. Dewhirst are well-established, capable individuals who are dedicated to pushing the boundaries of dental research. After the mentored phase of this K99, Dr. Bor's career goal is to become a tenure-track faculty member at a leading academic research institute, where he can further develop his research program on CPR bacteria while mentoring and educating students. Dr. Bor's proposed work will provide key insights into the physiology and pathogenesis of this unique group of host-associated bacteria and may contribute to the development of novel therapeutic tools for treating periodontitis.