结核分枝杆菌免疫原菌株 CD11_6 的基因组分析及其在激活针对结核分枝杆菌的 T 细胞中的潜在作用。

A genomic analysis of Mycobacterium immunogenum strain CD11_6 and its potential role in the activation of T cells against Mycobacterium tuberculosis.

机构信息

Immunology Laboratory, CSIR- Institute of Microbial Technology, Chandigarh, India.

Centre for Biomedical Engineering, Indian Institute of Technology, Ropar, India.

出版信息

BMC Microbiol. 2019 Mar 20;19(1):64. doi: 10.1186/s12866-019-1421-y.

DOI:10.1186/s12866-019-1421-y

PMID:30894125

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6425668/

Abstract

BACKGROUND

Mycobacterium tuberculosis (Mtb) is an etiological agent of tuberculosis (TB). Tuberculosis is a mounting problem worldwide. The only available vaccine BCG protects the childhood but not adulthood form of TB. Therefore, efforts are made continuously to improve the efficacy of BCG by supplementing it with other therapies. Consequently, we explored the possibility of employing Mycobacterium immunogenum (Mi) to improve BCG potential to protect against Mtb.

RESULTS

We report here the genome mining, comparative genomics, immunological and protection studies employing strain CD11_6 of Mi. Mycobacterium immunogenum was isolated from duodenal mucosa of a celiac disease patient. The strain was whole genome sequenced and annotated for identification of virulent genes and other traits that may make it suitable as a potential vaccine candidate. Virulence profile of Mi was mapped and compared with two other reference genomes i.e. virulent Mtb strain H37Rv and vaccine strain Mycobacterium bovis (Mb) AFF2122/97. This comparative analysis revealed that Mi is less virulent, as compared to Mb and Mtb, and contains comparable number of genes encoding for the antigenic proteins that predict it as a probable vaccine candidate. Interestingly, the animals vaccinated with Mi showed significant augmentation in the generation of memory T cells and reduction in the Mtb burden.

CONCLUSION

The study signifies that Mi has a potential to protect against Mtb and therefore can be a future vaccine candidate against TB.

摘要

背景

结核分枝杆菌（Mtb）是结核病（TB）的病原体。结核病是一个全球性的日益严重的问题。唯一可用的卡介苗（BCG）疫苗可以保护儿童免受结核病的侵害，但不能保护成年人。因此，人们不断努力通过补充其他疗法来提高 BCG 的疗效。因此，我们探索了使用分枝杆菌免疫原（Mi）来提高 BCG 预防 Mtb 的潜力的可能性。

结果

我们在此报告使用 Mi 的 CD11_6 株进行基因组挖掘、比较基因组学、免疫学和保护研究。分枝杆菌免疫原从乳糜泻患者的十二指肠黏膜中分离出来。对该菌株进行了全基因组测序和注释，以鉴定可能使其成为潜在疫苗候选物的毒力基因和其他特征。Mi 的毒力谱进行了绘制，并与另外两个参考基因组（即毒力 Mtb 菌株 H37Rv 和疫苗株 Mycobacterium bovis（Mb）AFF2122/97）进行了比较。这项比较分析表明，Mi 的毒力比 Mb 和 Mtb 低，并且编码抗原蛋白的基因数量相当，这表明它可能是一种潜在的疫苗候选物。有趣的是，用 Mi 接种的动物显示出记忆 T 细胞生成显著增加，Mtb 负担减少。