Impact of Mycobacterium tuberculosis genotype and host ancestry on strain transmissibility

结核病是一种由结核分枝杆菌引起的疾病，每年造成的死亡人数超过任何其他单一传染病。细菌谱系的全球地理分布表明，某些谱系的菌株与人类宿主共同适应了一个漫长的进化轨迹。目前尚不清楚哪种细菌谱系和宿主祖先的组合更有可能发展为活动性结核病，从而传播疾病。利用来自一个国际联盟的流行病学和全基因组测序数据，该项目旨在通过多元回归模型调查传播性结核病病例中细菌谱系与人类祖先之间的关系。为了获得细菌致病原因的生物学见解，将采用全基因组关联方法来鉴定与遗传表型相关的遗传位点。研究细菌菌株与其人类宿主之间的共同适应和共同进化将有助于阐明结核感染的病理生物学，并有助于确定最容易传播的细菌谱系和宿主祖先的组合。这最终有助于在人类流动和全球化加剧的时代完善疾病控制战略。

Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis and is responsible for more deaths annually than any other single infectious agent. The global geographical distribution of the bacterial lineages suggests a long evolutionary trajectory whereby strains of certain lineages have co-adapted with their human hosts. It remains unknown which combinations of bacterial lineage and host ancestry are more likely to develop active TB and thus transmit disease. Using epidemiological and whole genome sequencing data from an international consortium, this project aims to investigate the relationship between bacterial lineage and human ancestry among transmitted TB cases through multivariate regression modelling. To gain biological insight into bacterial causes of variable transmissibility, a genome wide association approach will be employed to identify genetic loci associated with the transmissibility phenotype. Investigating the co-adaptation and co-evolution between the bacterial strains and their human host will shed light on the pathobiology of TB infection, and help identify combinations of bacterial lineage and host ancestry that are most prone to transmit. This can ultimately help refine disease containment strategies in an era of increased human movement and globalization.