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

基本信息

批准号：
10559532
负责人：
Xuesong He
金额：
$ 48.27万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10559532
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 Learning 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

项目摘要

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具有的超小寄生细菌基因组极大减少，并显示出牙龈炎和牙周炎的丰度增加。在上一个融资周期，我们成功地培养和测序了TM7X，这是未经文化的TM7的第一个成员人类的门。菌株TM7X在所有细菌中都是独特的，它具有超巨大的大小（200-300 nm），并且生活在宿主细菌的表面，这种关系从未在人类微生物组中报道过或在细菌域中。 TM7X具有高度降低的基因组，无法合成其自身的任何氨基酸，维生素或细胞壁前体，必须寄生其他口服细菌，从而影响其生长。特别请注意，TM7属于候选门（CPR），这是最近发现的细分域细菌占已知细菌多样性的26％，估计为70个未培养的门基因组减少。迄今为止，TM7X仍然是整个CPR中唯一报告的培养代表使我们的团队处于独特的位置，以在该领域取得重大进步并促进基本这些超小型人相关细菌以及整个心肺复苏群体的发现。我们的初步数据表明，TM7X及其细菌宿主的关系是口服放线菌的关系 odontolyticus菌株XH001是一种高度调节的共生相互作用，其中TM7X显示两个共生相（与宿主共存）和毒性寄生相（诱导宿主细胞死亡）。这种有趣的关系类似于温带噬菌体及其宿主观察到的噬菌体能够在溶菌发生和裂解周期之间切换，并需要生理和生态后果。在这个应用，我们旨在实现以下两个目标。 1）确定分子成分和调节管理TM7X与其主机之间关系的途径； 2）研究细菌的范围 TM7X与。特别是，宿主杀死的机制在细菌寄生虫中编码减少的基因组既有新颖，又是临床上的。感染和杀死多重的能力细菌宿主可以允许TM7X影响口腔社区的动态和结构，从而调节在健康和疾病期间，社区和影响微生物组。这项研究的成功将大大推动这些超小细菌的发展研究领域，扩展我们对人类发现的新型微生物共生的知识，以及 CPR生物学生物学生态学。

项目成果

期刊论文数量（52）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host.

DOI：
10.1073/pnas.1810625115
发表时间：
2018-11-27
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Bor B;McLean JS;Foster KR;Cen L;To TT;Serrato-Guillen A;Dewhirst FE;Shi W;He X
通讯作者：
He X

Phenotypic and Physiological Characterization of the Epibiotic Interaction Between TM7x and Its Basibiont Actinomyces.

DOI：
10.1007/s00248-015-0711-7
发表时间：
2016-01
期刊：
Microbial ecology
影响因子：
3.6
作者：
Bor B;Poweleit N;Bois JS;Cen L;Bedree JK;Zhou ZH;Gunsalus RP;Lux R;McLean JS;He X;Shi W
通讯作者：
Shi W

Human variation in gingival inflammation.

DOI：
10.1073/pnas.2012578118
发表时间：
2021-07-06
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Bamashmous S;Kotsakis GA;Kerns KA;Leroux BG;Zenobia C;Chen D;Trivedi HM;McLean JS;Darveau RP
通讯作者：
Darveau RP

Quorum Sensing Modulates the Epibiotic-Parasitic Relationship Between Actinomyces odontolyticus and Its Saccharibacteria epibiont, a Nanosynbacter lyticus Strain, TM7x.

DOI：
10.3389/fmicb.2018.02049
发表时间：
2018
期刊：
Frontiers in microbiology
影响因子：
5.2
作者：
Bedree JK;Bor B;Cen L;Edlund A;Lux R;McLean JS;Shi W;He X
通讯作者：
He X

Host translation machinery is not a barrier to phages that interact with both CPR and non-CPR bacteria.

DOI：
10.1128/mbio.01766-23
发表时间：
2023-12-19
期刊：
MBIO
影响因子：
6.4
作者：
Liu, Jett;Jaffe, Alexander L.;Chen, Linxing;Bor, Batbileg;Banfield, Jillian F.
通讯作者：
Banfield, Jillian F.