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

Abdallah Abdallah, Grant A. Hill-Cawthorne, Thomas D. Otto, Francesc Coll, José Afonso Guerra-Assunção, Ge Gao, Raeece Naeem, Hifzur Rahman Ansari, Tareq Majed Yasin Malas, Sabir Adroub, Theo Verboom, Roy Ummels, Huoming Zhang, Aswini Kumar Panigrahi, Ruth McNerney, Roland Brosch, Taane G. Clark, Marcel A. Behr, Wilbert Bitter, Arnab Pain

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43 Scopus citations

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.
Original languageEnglish (US)
JournalScientific Reports
Volume5
Issue number1
DOIs
StatePublished - Oct 21 2015

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