兼性胞内寄生菌宿主生态位适应标识的筛选和鉴定：以巴尔通体为研究对象

微生物跨物种传播是引发传染病暴发流行的原因之一，探讨寄生过程的适应机制、找到关键分子标识对于人和动物传染病诊断、药物研发和致病机制等研究和防治具有重要意义。巴尔通体是一群革兰阴性、兼性胞内寄生菌，在哺乳动物中广泛流行，引起多种人兽共患病，多因素使其呈高度遗传多样性，是研究病原细菌与宿主相互作用、适应进化和病原溢出效应的理想模型。细菌适应进化不仅与基因变异和水平转移有关，还受到转录调控和表观修饰的影响，为揭示巴尔通体宿主适应机制、找到宿主生态位适应标识HNASs，本研究拟应用二代和三代SMRT高通量测序技术进行多宿主来源的巴尔通体大种群基因组测序及GWAS分析，筛选基因组水平的HNASs；再选择差异宿主来源的代表菌株进行RNA-seq和关联分析，比较和验证基因组和转录调控水平HNASs的变化差异；最后，预测分析基因组甲基化相关基因和位点与适应的关联，探索表观遗传修饰对细菌宿主适应的潜在作用。

Microbial cross-species transmission is one of the causes of outbreaks of infectious diseases. Deciphering the adaptation mechanisms of parasitic processes and the identification of key molecular genetic signatures are of important significance for understanding the biological mechanisms associated with a successful switch to new host species, including critical host–pathogen interactions that may represent novel diagnostic and therapeutic targets, as well as pathogenesis. Bartonellae is a group of Gram-negative, facultative intracellular parasites that are highly prevalent in mammals and can cause a variety of zoonotic diseases. Bartonellae show a highly genetically diverse owing to intricate environmental factors from habitats which makes it an ideal model for observing the pathogen-host interactions, adaptive evolution and spillover effects of pathogens. The adaptive evolution of bacteria is not only depending on gene mutations and horizontal transfers, but also affected by transcriptional regulation and epigenetic modifications. In order to reveal the adaptation mechanism of Bartonellae and identifying the host niche adaptation signatures (HNASs), we intend to apply the NGS and PacBio SMRT high-throughput sequencing technologies for whole genome sequencing of the Bartonellae large population of multi-host sources and GWAS analysis to screen genomic level HNASs; then select representative strains from different host sources for RNA-seq and biological correlation analysis, compare and verify the differences of HNASs between the genomic level and transcription regulation. Finally, to explore the potential role of epigenetic modifications in the bacterial host adaptation, sequencing the methylome and predictive analysis of the association between genomic methylation-related genes and modification loci and the host adaptation will be carried out.