Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.
Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.
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DOI：
10.1038/srep15443
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发表时间：
2015-10-21
影响因子：
4.6
通讯作者：
Pain A
中科院分区：
文献类型：
--
作者：
Abdallah AM;Hill-Cawthorne GA;Otto TD;Coll F;Guerra-Assunção JA;Gao G;Naeem R;Ansari H;Malas TB;Adroub SA;Verboom T;Ummels R;Zhang H;Panigrahi AK;McNerney R;Brosch R;Clark TG;Behr MA;Bitter W;Pain A
虽然预防结核病的卡介苗疫苗已有90多年的历史，但由于保护效果不一和缺乏持久的记忆反应，其有效性受到了阻碍。造成这种差异的一个因素可能是世界各地使用的卡介苗菌株的多样性，部分原因是疫苗生产过程中积累的基因组变化及其导致的基因表达差异。我们以单碱基对分辨率比较了全球收集的14种最广泛使用的卡介苗菌株的基因组和转录组。我们还使用定量蛋白质组学来确定四个串联重复（DU）组的五个代表性卡介苗菌株之间蛋白质表达的关键差异。我们提供了14个卡介苗菌株的单核苷酸多态性（snp）、拷贝数变异和插入和缺失（indel）的综合图谱。全基因组SNP表征允许构建一个新的和强大的卡介苗株系统发育谱系。转录和蛋白质组学分析揭示了卡介苗菌株的代谢重塑，这可能反映在免疫原性改变和可能的疫苗效力上。总之，这些综合组学数据代表了全球卡介苗菌株收集中最全面的遗传变异目录。
Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.