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

口腔TM7菌株（第一个培养的超小型细菌）的分子和病​​原学研究

• 批准号: 10308387
• 负责人: Batbileg Bor
• 金额: $ 24.9万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-13 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308387
• 关键词: Actinomyces odontolyticus; Address; Affect; Area; Bacteria; Biodiversity; Biological Models; Biology; Cell Death; Cell Size; Cell physiology; Cells; Characteristics; Coculture Techniques; Cross Infection; Data; Dental Research; Development; Disease; Disease Outcome; Environment; Essential Genes; Faculty; Fellowship; Foundations; Future; Genetic; Genome; Genomics; Goals; Human; Human body; Immunity; In Vitro; Individual; Inflammatory; Investigation; Knowledge; Libraries; Life Style; Light; Link; Mentors; Metabolic; Metagenomics; Methods; Molecular; Mucous Membrane; Mus; Mutagenesis; National Institute of Dental and Craniofacial Research; Oral; Oral cavity; Organism; Parasites; Pathogenesis; Pathogenicity; Periodontal Diseases; Periodontitis; Phase; Phenotype; Physiological; Physiology; Positioning Attribute; Radiation; Research; Research Institute; Research Personnel; Rest; Role; Site; Solid; Students; Surface; Testing; Training; Work; base; behavioral phenotyping; career; design; experience; genetic signature; genomic signature; grasp; host-associated microbial communities; human disease; in vivo; insight; macrophage; member; microbial; mutant; novel; novel therapeutics; oral bacteria; oral microbiome; programs; public health relevance; research study; skills; tenure track; tissue culture; tool; transcriptomics

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.

项目概要/摘要 增加我们对与人类相关的尚未培养的细菌的了解对于 了解它们在人类疾病中的潜在作用。 TM7 门就是这样的一组细菌。 尽管它在环境和人体部位中无处不在并且具有潜力 由于牙周炎的影响，直到非常时期才分离出 TM7 门的可培养代表。 最近。此外，TM7属于新描述的候选门辐射（CPR）细菌， 其中包含> 15％（> 35个门）的整个细菌域并且缺乏分离的代表。 值得注意的是，CPR 生物体具有其他细菌领域所不存在的独特生物学特性， 其中包括但不限于超小细胞尺寸（200-500nm）和减少的基因组（<1Mb） 代谢能力受到高度限制。我们的实验室分离出第一个人类口腔 TM7 物种 (TM7x) 作为 生活在宿主细菌 XH001（口腔放线菌）表面的专性表生寄生虫 溶齿菌菌株）。该提案使用 TM7x/XH001 作为模型系统，旨在实现三个目标 基础知识差距：（1）控制该现象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的作用是什么？最终目标是 揭开TM7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 博士的博士后研究致力于描述生理学和 TM7x/XH001 相互作用的表型行为，以及因此的机制和致病性研究 TM7 细菌是他的研究的合理延伸。拟议的 K99/R00 研究旨在 补充Bor博士之前的研究经验，并对他进行所需的技术和知识方面的培训 成为独立调查员的技能。 Bor 博士将在领先的研究机构之一接受培训 研究所、加州大学洛杉矶分校。他的主要导师石博士以及共同导师何博士、McLean 博士和 Dewhirst 博士是 信誉卓著、有能力的个人，致力于突破牙科研究的界限。 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授 在一家领先的学术研究机构，他可以进一步发展他的心肺复苏研究项目 在指导和教育学生的同时消灭细菌。 Bor 博士提出的工作将提供以下方面的重要见解： 这一独特的宿主相关细菌群的生理学和发病机制，可能有助于 开发治疗牙周炎的新型治疗工具。