创伤弧菌毒力相关因子的全基因组关联分析研究

Genome-wide association study on virulence factors of Vibrio vulnificus

摘要:

[目的] 创伤弧菌是致死率最高的弧菌物种，但目前尚无在全基因组层面挖掘毒力相关因子的研究。本研究以创伤弧菌分离来源（临床和环境）作为不同表型，通过与260株基因组序列进行关联分析，挖掘毒力相关因子，从而进一步了解创伤弧菌致病因素。[方法] 对139株创伤弧菌分离株进行高通量测序，获取其全基因组序列；与公共数据库已公开发表的121株基因组整合，使用pyseer软件进行全基因组关联分析，对与不同分离来源显著相关的基因进行注释和解读。[结果] 共发现11个基因与临床分离株显著相关，其中9个是本研究新发现的创伤弧菌潜在毒力相关因子。[结论] 本研究使用群体基因组学和统计遗传学方法，在全基因组范围扫描挖掘了创伤弧菌毒力相关因子，为深入揭示该物种致病机制、设计新的疫苗和治疗靶点提供了重要依据。

Abstract:

[Objective] Vibrio vulnificus is a pathogen with the highest mortality in Vibrio genus. However, currently there is lacking knowledge of virulence-associated factors across the whole genome wide for this species. By using bacterial genome-wide association study (BGWAS), we investigated the genes that are related with different sources (clinical/environment) of V. vulnificus isolates, aiming to provide further understanding on genetic factors that potentially influence its pathogenicity. [Methods] In total 260 V. vulnificus genomes were analyzed, including 139 newly sequenced in this study and 121 published genomes. We identified the genomes variations, including SNPs and accessory genes from the dataset, and then by using software pyseer, we determined the associations between sources of isolates and SNPs, genes, and Kmers, separately. We annotated the function of the statistically significant genes and inferred their possible influence on virulence of the bacteria. [Results] We found that 11 genes to be significantly correlated with clinical isolates of V. vulnificus, among which 9 were newly identified in this study.[Conclusion] By using methods of population genomics and statistical genetics, we screened the potential virulence-associated factors of V. vulnificus across the whole genome. Our findings provided new targets on vaccine designing and drug development, and would help to get further insight on pathogenic mechanism of this pathogen.