Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

Citations Over TimeTop 10% of 2015 papers

Abstract

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.

Related Papers

• → Estimating the size of the bacterial pan-genome(2009)357 cited
• → Differentiation and inter-genomic relationships among C, E and D genomes in the Oryzaofficinalis complex (Poaceae) as revealed by multicolor genomic in situ hybridization(2001)38 cited
• → Identification of signals required for the insertion of heterologous genome segments into the reovirus genome.(1995)23 cited
• → Genomic relationships of N-genome Triticum species(1992)17 cited
• → Sequencing of Chloroplast Genome in Sesame(2021)1 cited