Domestication and characterization of TM7-the most elusive oral phylum

TM7——最难以捉摸的口腔门的驯化和表征

• 批准号: 10021218
• 负责人: Xuesong He
• 金额: $ 14.26万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021218
• 关键词: Actinomyces odontolyticus; Affect; Amino Acids; Bacteria; Bacterial Physiology; Bacteriophages; Biological; Cell Death; Cell Wall; Clinical; Communities; Cytolysis; Data; Dental Plaque; Disease; Ecology; Environment; Funding; Genes; Genetic study; Genome; Gingivitis; Goals; Growth; Health; Horizontal Disease Transmission; Human; Human Microbiome; Imaging Techniques; Investigation; Knowledge; Laboratories; Life Style; Lytic Phase; Maintenance; Molecular; Names; Nutrient; Oral; Oral Microbiology; Oral cavity; Organism; Outcome; Paper; Parasites; Periodontitis; Phase; Physiological; Positioning Attribute; Process; Progress Reports; Publishing; Radiation; Regulatory Pathway; Reporting; Research; Role; Sampling; Site; Structure; Surface; Symbiosis; Testing; Virulent; Vitamins; clinically relevant; genetic approach; member; microbial; microbiome; multiple omics; novel; oral bacteria; oral microbiome; programs; success

Abstract The overall goal of this application is to characterize newly discovered ultra-small parasitic bacteria that have extremely reduced genomes and show increased abundance in gingivitis and periodontitis. In the previous funding cycle, we successfully cultivated and sequenced TM7x, the first member of the uncultivated TM7 phylum from humans. Strain TM7x is unique among all bacteria, it has an ultrasmall size (200-300 nm) and lives on the surface of a host bacterium, a relationship that had never been reported in the human microbiome or in the Bacteria domain. With a highly-reduced genome, TM7x cannot synthesize any of its own amino acids, vitamins or cell wall precursors and must parasitize other oral bacteria which impacts their growth. Of particular note is that TM7 belongs to the Candidate Phyla Radiation (CPR), a recently discovered subdivision in the domain Bacteria that comprises >26% of the known bacterial diversity with an estimated 70 uncultivated Phyla with reduced genomes. To date, TM7x is still the only reported cultivated representative of the entire CPR, putting our team in a unique position to make significant advancements in the field and facilitate fundamental discoveries on these ultra-small human associated bacteria, as well as the CPR group as a whole. Our preliminary data revealed that the relationship of TM7x and its bacterial host, an oral Actinomyces odontolyticus strain XH001 is a highly-regulated symbiotic interaction in which TM7x displays both symbiotic phase (co-existing with host) and virulent parasitic phase (inducing host cell death). This intriguing relationship is similar to the one observed for temperate bacteriophages and their hosts where phages are capable of switching between lysogenic and lytic cycle, and entails physiological and ecological consequences. In this application, we aim to achieve the following two goals. 1) To identify the molecular components and regulatory pathways governing the relationship between TM7x and its host; 2) To investigate the range of bacteria that TM7x interacts with. In particular, the mechanism of host killing encoded within a bacterial parasite with a reduced genome is both fundamentally novel and clinically relevant. The ability to infect and kill multiple bacterial hosts may allow TM7x to influence the oral community dynamics and structure, thus modulating community and impacting microbiome during health and diseases. The success of the study would greatly advance the developing research field of these ultra-small bacteria, expand our knowledge on this novel microbial symbiosis found in humans, as well as the potential impact of CPR organisms on oral microbiome ecology.

抽象的 该应用的总体目标是表征新发现的超小型寄生细菌，这些细菌具有 基因组极度减少，并且牙龈炎和牙周炎的基因组丰度增加。在之前的 资金周期内，我们成功培养并测序了TM7x，这是未培养的TM7的第一个成员 来自人类的门。 TM7x 菌株在所有细菌中是独一无二的，它具有超小尺寸（200-300 nm）并且 生活在宿主细菌的表面，这种关系在人类微生物组中从未有过报道 或在细菌领域。由于基因组高度减少，TM7x 无法合成任何自己的氨基酸， 维生素或细胞壁前体，并且必须寄生其他影响其生长的口腔细菌。特别是 请注意，TM7 属于候选放射门 (CPR)，这是最近在放射学中发现的一个分支。 包含 >26% 已知细菌多样性的细菌，估计有 70 个未培养的门 基因组减少。迄今为止，TM7x仍然是整个CPR唯一报道的栽培代表， 使我们的团队处于独特的地位，可以在该领域取得重大进步并促进基础设施建设 关于这些超小型人类相关细菌以及整个心肺复苏组的发现。 我们的初步数据揭示了 TM7x 与其细菌宿主（一种口腔放线菌）的关系 溶齿菌菌株 XH001 是一种高度调控的共生相互作用，其中 TM7x 表现出共生 阶段（与宿主共存）和剧毒寄生阶段（诱导宿主细胞死亡）。这种有趣的关系 类似于在温带噬菌体及其宿主中观察到的情况，其中噬菌体能够 溶原循环和裂解循环之间的切换，并带来生理和生态后果。在这个 应用中，我们旨在实现以下两个目标。 1) 识别分子成分和调控 控制 TM7x 与其宿主之间关系的途径； 2) 调查细菌的范围 TM7x 交互。特别是，细菌寄生虫内编码的宿主杀死机制 减少基因组既具有根本新颖性又具有临床相关性。具有感染和杀死多人的能力 细菌宿主可能允许 TM7x 影响口腔群落动态和结构，从而调节 社区以及在健康和疾病期间影响微生物组。 该研究的成功将极大地推进这些超小细菌研究领域的发展， 扩大我们对人类中发现的这种新型微生物共生关系的了解，以及其潜在影响 CPR 生物对口腔微生物生态学的影响。