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通过群体基因组学鉴定 潜在的致病靶点和生存策略。

Identification of potential pathogenic targets and survival strategies of through population genomics.

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.

Shenzhen Center for Disease Control and Prevention, Shenzhen, China.

出版信息

Front Cell Infect Microbiol. 2023 Aug 25;13:1254379. doi: 10.3389/fcimb.2023.1254379. eCollection 2023.

Abstract

, a foodborne pathogen, has a high mortality rate. Despite its relevance to public health, the identification of virulence genes associated with the pathogenicity of currently known clinical isolates of is incomplete and its synergistic pathogenesis remains unclear. Here, we integrate whole genome sequencing (WGS), genome-wide association studies (GWAS), and genome-wide epistasis studies (GWES), along with phenotype characterization to investigate the pathogenesis and survival strategies of . GWAS and GWES identified a total of six genes (, , , , , and ) associated with the pathogenicity of clinical isolates related to nucleotide/amino acid transport and metabolism, cell membrane biogenesis, signal transduction mechanisms, and protein turnover. Of these, five were newly discovered potential specific virulence genes of in this study. Furthermore, GWES combined with phenotype experiments indicated that isolates were clustered into two ecological groups (EGs) that shared distinct biotic and abiotic factors, and ecological strategies. Our study reveals pathogenic mechanisms and their evolution in to provide a solid foundation for designing new vaccines and therapeutic targets.

摘要

创伤弧菌,一种食源性病原体,具有很高的死亡率。尽管它与公共卫生有关,但与目前已知的临床创伤弧菌分离株的致病性相关的毒力基因的鉴定并不完整,其协同发病机制仍不清楚。在这里,我们整合了全基因组测序(WGS)、全基因组关联研究(GWAS)和全基因组上位性研究(GWES),以及表型特征分析,以研究创伤弧菌的发病机制和生存策略。GWAS 和 GWES 总共鉴定出了 6 个与与核苷酸/氨基酸转运和代谢、细胞膜生物发生、信号转导机制和蛋白质周转相关的临床分离株的致病性相关的基因(、、、、、和)。其中,有 5 个是本研究中新发现的创伤弧菌潜在特异性毒力基因。此外,GWES 结合表型实验表明,创伤弧菌分离株被分为两个生态群(EG),它们具有不同的生物和非生物因素以及生态策略。我们的研究揭示了创伤弧菌的发病机制及其进化,为设计新的疫苗和治疗靶点提供了坚实的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3159/10485832/a58007f693d0/fcimb-13-1254379-g001.jpg

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