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肉毒梭菌的泛基因组分析揭示了药物开发的独特靶点。

Pan-genome analysis of Clostridium botulinum reveals unique targets for drug development.

作者信息

Bhardwaj Tulika, Somvanshi Pallavi

机构信息

Department of Biotechnology, TERI University, 10, Industrial area, Vasant Kunj, New Delhi 110070, India.

Department of Biotechnology, TERI University, 10, Industrial area, Vasant Kunj, New Delhi 110070, India.

出版信息

Gene. 2017 Aug 5;623:48-62. doi: 10.1016/j.gene.2017.04.019. Epub 2017 Apr 24.

DOI:10.1016/j.gene.2017.04.019
PMID:28450142
Abstract

Clostridium botulinum, a formidable pathogen is responsible for the emerging cause of food poisoning cases on the global canvas. The endemicity of bacterium Clostridium botulinum is reflected by the sudden hospital outbreaks and increased resistance towards multiple drugs. Therefore, a combined approach of in-silico comparative genomic analysis with statistical analysis was applied to overcome the limitation of bench-top technologies. Owing to the paucity of genomic data available by the advent of third generation sequencing technologies, several 'omics' technologies were applied to understand the underlying evolutionary pattern and lifestyle of the bacterial pathogen using phylogenomics. The calculation of pan-genome, core genome and singletons provides view of genetic repertoire of the bacterial pathogen lineage at the successive level, orthology shared and specific gene subsets. In addition, assessment of pathogenomic potential, resistome, toxin/antitoxin family in successive pathogenic strains of Clostridium botulinum aids in revealing more specific targets for drug design and development.

摘要

肉毒梭菌是一种可怕的病原体,是全球范围内食物中毒病例不断增加的原因。肉毒梭菌的地方性流行表现为医院突然爆发疫情以及对多种药物的耐药性增加。因此,采用了计算机模拟比较基因组分析与统计分析相结合的方法来克服传统实验技术的局限性。由于第三代测序技术出现时可用的基因组数据匮乏,因此应用了多种“组学”技术,通过系统发育基因组学来了解这种细菌病原体的潜在进化模式和生活方式。泛基因组、核心基因组和单拷贝基因的计算,能在连续水平上提供细菌病原体谱系的遗传信息库视图、共享的直系同源基因和特定基因子集。此外,对肉毒梭菌连续致病菌株的致病基因组潜力、耐药基因组、毒素/抗毒素家族进行评估,有助于揭示药物设计和开发的更具体靶点。

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