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

项目概要/摘要 增加我们对人类相关的尚未培养的细菌的了解是至关重要的， 了解它们在人类疾病中的潜在作用。TM 7门就是这样一组细菌。 尽管它在环境和人体部位无处不在， 由于TM 7在牙周炎中的重要性，直到很久以前，还没有分离出TM 7门的可培养代表。 最近此外，TM 7属于新描述的候选辐射门（CPR）细菌， 其包含>15%（>35门）的整个细菌结构域并且缺乏分离的代表。 值得注意的是，CPR生物体具有独特的生物学特性，而这种生物学特性在细菌的其他领域中是不存在的， 包括但不限于超小细胞尺寸（200- 500 nm）和简化基因组（<1 Mb）， 高度受限的代谢能力我们的实验室分离了第一个人类口腔TM 7物种（TM 7 x）， 一种生活在其宿主细菌XH 001（一种口腔放线菌）表面的专性表生寄生虫 溶牙菌菌株）。以TM 7 x/XH 001为模型系统，该方案旨在实现三个目标： 基本的知识差距：（1）什么是具体的分子机制，管理 TM 7 x与宿主菌的相互作用(2)相同的规则和机制是否适用于所有TM 7 会员？(3)TM 7在人类粘膜炎性疾病中的作用是什么？最终目标是 揭开TM 7和其他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博士的博士后研究工作主要是描述生理和 TM 7 x/XH 001相互作用的表型行为，因此， TM 7细菌是他研究的合理延伸。拟议的K99/R 00研究旨在 补充博尔博士先前的研究经验，并在必要的技术和知识方面对他进行培训 成为一名独立调查员。博尔博士将在一个领先的研究机构接受培训， 加州大学洛杉矶分校。他的主要导师，施博士，以及共同导师，何博士，姆克林博士和Dewhirst博士是 有能力的人，致力于推动牙科研究的界限。 在K99的指导阶段之后，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术研究计划 细菌，同时指导和教育学生。Bor博士的工作将提供关键的见解， 这组独特的宿主相关细菌的生理学和发病机制，并可能有助于 开发治疗牙周炎的新型治疗工具。

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.