Human adaptation and transmissibility of Mycobacterium tuberculosis genetic lineages. A genomic epidemiology study to guide TB control

结核分枝杆菌遗传谱系的人类适应和传播性。

• 批准号: 10382446
• 负责人: Maha Farhat
• 金额: $ 25.1万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-05 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382446
• 关键词: American; Bacteria; Biological; Biological Response Modifiers; Biology; Cause of Death; Cessation of life; Characteristics; Chemoprophylaxis; Clinical; Communicable Diseases; Contact Tracing; Containment; Country; Coupled; DNA; Data; Disease; Disease Progression; Drug resistance; East Asian; Epidemiology; Exposure to; Genes; Genetic; Genetic study; Genotype; Geography; Goals; Human; Immune response; Infection; Infectious Agent; Intercistronic Region; International; Link; Maps; Measures; Modeling; Movement; Mutation; Mycobacterium tuberculosis; Patients; Pattern; Phenotype; Population Surveillance; Positioning Attribute; Proteins; Public Health; Regulator Genes; Research Personnel; Resolution; Risk; Role; Societies; Statistical Models; System; Time; Tuberculosis; Virulence; Work; base; case control; cytokine; design; disease phenotype; disease transmission; disorder control; epidemiologic data; epidemiology study; genetic variant; genome sequencing; genome wide association study; genomic epidemiology; genomic locus; high risk; human pathogen; improved; in vitro Assay; in vitro Model; indexing; innovation; latent infection; novel; pathogen; pathogen genome; stem; surveillance data; tool; transmission process; vaccine development; whole genome

The main causative agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), is responsible for more deaths annually than any other single infectious agent. Mtb bacteria are separated into eight genetic lineages and preliminary data supports differences in virulence and transmissibility among them. Globally, Mtb lineages show distinct geographical patterns that parallel that of human subpopulations suggesting co-adaption between host and pathogen. It is unknown if this geographic pattern will continue to be observed in cosmopolitan societies where different human subpopulations live in close proximity, and Mtb lineages have the opportunity to infect ‘naive’ hosts without co-adaptation. Assessing if and why Mtb lineages have variable transmissibility and if they are indeed adapted to different human subpopulations can help guide disease control and improve our understanding of biological host pathogen relationships. Using epidemiological and whole genome sequencing data from an international consortium, this project aims to investigate the relationship between Mtb lineage and disease transmissibility across and within human subpopulations. A genome wide association approach will be employed to fine map specific Mtb genetic loci associated with the transmissibility phenotype. Investigating adaptation between Mtb and its human host will define combinations of Mtb lineage and host ancestry most prone to progression and transmission. This can ultimately help refine disease containment strategies such as latent TB chemoprophylaxis and targeted contact tracing to achieve WHO End TB goals of eliminating TB by 2035.

结核病（TB），结核分枝杆菌（MTB）的主要灾难性药物比任何其他单一的感染剂造成的死亡人数更多。 MTB细菌分为八个遗传谱系，初步数据支持病毒的差异及其可递移性。在全球范围内，MTB谱系显示出独特的地理模式，这些模式与人类亚群的平行表明，表明宿主和病原体之间的共同适应。尚不清楚这种地理模式是否会在国际大都会社会中继续观察到，在这种社会中，不同的人类亚群体处于近距离状态，而MTB血统有机会在没有共同适应的情况下感染“天真”宿主。评估MTB谱系是否具有可变的传播以及它们是否确实适应不同的人类亚群可以帮助指导疾病控制并提高我们对生物宿主病原体关系的理解。该项目使用来自国际财团的流行病学和整个基因组测序数据，旨在研究MTB谱系与人类亚群体之间和内部疾病传播之间的关系。将采用一种基因组广泛的关联方法来细微地图特定的MTB遗传局部与传输表型相关。调查MTB及其人类宿主之间的适应性将定义MTB谱系的组合和最容易进展和传播的宿主血统。这最终可以帮助完善疾病遏制策略，例如潜在的TB化学预防和靶向接触追踪，以实现谁在2035年结束TB的目标。