Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations.
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.
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Abdallah M
AM
Abdallah
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.|Marie Bashir Institute for Infectious Diseases and Biosecurity and School and Public Health, University of Sydney, NSW 2006, Australia.
Grant A
GA
Hill-Cawthorne
Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.
Thomas D
TD
Otto
Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.
Francesc
F
Coll
Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.
José Afonso
JA
Guerra-Assunção
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Ge
G
Gao
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Raeece
R
Naeem
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Hifzur
H
Ansari
Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Jeddah, Kingdom of Saudi Arabia.
Tareq B
TB
Malas
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Sabir A
SA
Adroub
Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Theo
T
Verboom
Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Roy
R
Ummels
Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Huoming
H
Zhang
Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.
Aswini Kumar
AK
Panigrahi
Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.
Ruth
R
McNerney
Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France.
Roland
R
Brosch
Faculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, London, United Kingdom.|Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Taane G
TG
Clark
Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.
Marcel A
MA
Behr
Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Wilbert
W
Bitter
Pathogen Genomics Group, Biological, Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Kingdom of Saudi Arabia.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, 001-0020, Japan.
Arnab
A
Pain
D000064:Acclimatization / Q000235:genetics; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics*; D002473:Cell Wall / Q000187:drug effects / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D005786:Gene Expression Regulation; D016680:Genome, Bacterial; D006801:Humans; D009163:Mycobacterium bovis / Q000187:drug effects / Q000472:pathogenicity; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D040901:Proteomics; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control
D001500:BCG Vaccine