Mapping Gene-by-Gene Single-Nucleotide Variation in 8,535 Mycobacterium tuberculosis Genomes: a Resource To Support Potential Vaccine and Drug Development.
Mapping Gene-by-Gene Single-Nucleotide Variation in 8,535 Mycobacterium tuberculosis Genomes: a Resource To Support Potential Vaccine and Drug Development.
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绘制8,535个结核分枝杆菌基因组中逐个基因的单核苷酸变异图：支持潜在疫苗和药物开发的资源。
DOI：
10.1128/msphere.01224-20
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发表时间：
2021-03-10
期刊：
影响因子：
4.8
通讯作者：
McNally A
中科院分区：
文献类型：
--
作者：
Papakonstantinou D;Dunn SJ;Draper SJ;Cunningham AF;O'Shea MK;McNally A
结核病（TB）每年造成数百万人死亡。更有效的疫苗和新的抗结核药物对控制这种疾病至关重要。大量的基因组学研究提高了我们对M.结核病耐药性、人口结构和传播模式。与此同时，反向疫苗学和药物发现管道已经确定了潜在的免疫原性候选疫苗或药物靶标。然而，更好地了解所有M.大规模研究结核病基因有助于确定新的疫苗和药物靶点。实现这一目标是目前研究的重点。基因组序列数据来自在线公共来源，涵盖7个M。结核病谱系。共对8,535个基因组序列进行了定位。结核病H37 Rv参考基因组，以鉴定单核苷酸多态性（SNP）。进一步处理初始定位的结果，并鉴定和进一步分析基因内核苷酸变体的频率分布。M.结核病H37 Rv基因组是保守的。具有最高水平保守性的基因通常与应激反应和维持氧化还原平衡有关。相反，具有高水平核苷酸变异的基因通常与耐药性相关。我们提供了所有M的单核苷酸变异的高分辨率分析。结核病基因跨越七个谱系，作为支持未来药物和疫苗开发的资源。我们已经确定了一些高度保守的基因，在M。结核病生物学，这可能会被用作新的候选疫苗和抗结核药物的目标。肺结核是一种由结核分枝杆菌引起的传染病。世纪上半叶，牛分枝杆菌卡介苗和抗结核药物的发现预示着结核病控制的新时代。然而，事实证明，防治结核病具有挑战性，特别是随着艾滋病毒和耐药性的出现。结核病控制的一个主要障碍是缺乏有效的疫苗，因为卡介苗的疗效因地域而异，对高危人群的肺部疾病几乎没有保护作用。我们的研究意义重大，因为它为支持未来的药物和疫苗开发提供了资源。我们通过更好地了解所有M.通过大规模研究结核病基因，并鉴定高度保守的基因，这些基因可能用作新型候选疫苗和抗结核药物的靶点。
Tuberculosis (TB) is responsible for millions of deaths annually. More effective vaccines and new antituberculous drugs are essential to control the disease. Numerous genomic studies have advanced our knowledge about M. tuberculosis drug resistance, population structure, and transmission patterns. At the same time, reverse vaccinology and drug discovery pipelines have identified potential immunogenic vaccine candidates or drug targets. However, a better understanding of the sequence variation of all the M. tuberculosis genes on a large scale could aid in the identification of new vaccine and drug targets. Achieving this was the focus of the current study. Genome sequence data were obtained from online public sources covering seven M. tuberculosis lineages. A total of 8,535 genome sequences were mapped against M. tuberculosis H37Rv reference genome, in order to identify single nucleotide polymorphisms (SNPs). The results of the initial mapping were further processed, and a frequency distribution of nucleotide variants within genes was identified and further analyzed. The majority of genomic positions in the M. tuberculosis H37Rv genome were conserved. Genes with the highest level of conservation were often associated with stress responses and maintenance of redox balance. Conversely, genes with high levels of nucleotide variation were often associated with drug resistance. We have provided a high-resolution analysis of the single-nucleotide variation of all M. tuberculosis genes across seven lineages as a resource to support future drug and vaccine development. We have identified a number of highly conserved genes, important in M. tuberculosis biology, that could potentially be used as targets for novel vaccine candidates and antituberculous medications. IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. In the first half of the 20th century, the discovery of the Mycobacterium bovis BCG vaccine and antituberculous drugs heralded a new era in the control of TB. However, combating TB has proven challenging, especially with the emergence of HIV and drug resistance. A major hindrance in TB control is the lack of an effective vaccine, as the efficacy of BCG is geographically variable and provides little protection against pulmonary disease in high-risk groups. Our research is significant because it provides a resource to support future drug and vaccine development. We have achieved this by developing a better understanding of the nucleotide variation of all of the M. tuberculosis genes on a large scale and by identifying highly conserved genes that could potentially be used as targets for novel vaccine candidates and antituberculous medications.