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; 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.

项目摘要/摘要 我们对与人类相关的尚未养殖细菌的了解至关重要 了解它们在人类疾病中的潜在作用。 TM7门是这样的细菌。 尽管在环境和人体站点中无处不在，并且潜力 在牙周炎中的影响，直到非常不可能隔离TM7门的可栽培代表 最近。此外，TM7属于新描述的候选门辐射（CPR）细菌， 它包括整个细菌结构域的> 15％（> 35个门），并且缺乏孤立的代表。 值得注意的是，CPR生物具有独特的生物学，这些生物学不存在于其他细菌领域， 其中包括但不限于超小细胞大小（200-500nm）和降低的基因组（<1MB） 高度限制的代谢能力。我们的实验室将第一个人类口服TM7种（TM7X）隔离为 偏向于宿主细菌XH001表面的特性表征寄生虫（口服放线菌 牙末菌株）。将TM7X/XH001作为模型系统，该提案旨在实现三个 基本知识差距：（1）控制该的特定分子机制是什么 TM7X与其宿主细菌之间的相互作用？ （2）执行相同的规则和机制适用于所有TM7 成员？ （3）TM7在人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，并真正掌握它们对人类的影响 疾病和环境。 Bor博士已经花费了他的博士后研究，以生理学和 TM7X/XH001相互作用的表型行为，因此，机械和致病性研究 TM7细菌是他研究的逻辑扩展。拟议的K99/R00研究旨在 补充博士博士先前的研究经验，并以所需的技术和智力培训他 成为独立调查员的技能。博士将在一项领先的研究之一接受培训 加州大学洛杉矶分校学院。他的主要导师什（Shi）博士和联合给出者He，McLean博士和Dewhirst博士是 建立良好，有能力的人致力于推动牙科研究的界限。 在此K99的指导阶段之后，博士的职业目标是成为终身教师 在一家领先的学术研究所，在那里他可以进一步制定有关CPR的研究计划 细菌指导和教育学生。 Bor博士的拟议工作将为您提供关键的见解 这一独特的宿主相关细菌的生理和发病机理，可能有助于 用于治疗牙周炎的新型治疗工具的开发。