Abstract:
BACKGROUND : Mycobacterium bovis BCG is a live, attenuated tuberculosis vaccine. While the vaccine
protects infants from tuberculosis, complications including disseminated infections have been reported
following vaccination. Genetically diverse BCG sub-strains now exist following continuous passaging of
the original Pasteur strain for vaccine manufacture. This genetic diversity reportedly influences the
severity of disseminated BCG infections and the efficacy of BCG immunization.
METHODS : M. bovis BCG was isolated from infants suspected of being infected with tuberculosis. The whole
genome of the clinical isolates and BCG Moscow were sequenced using Illumina Miseq and the sequences
were analysed using CLC Genomics Workbench 7.0, PhyResSE v1.0, and Parsnp.
RESULTS AND CONCLUSIONS : Genetic variations between the clinical strains and the reference BCG
Copenhagen were identified. The clinical strains shared only one mutation in a secretion protein.
Mutations were identified in various antibiotic resistance genes in the BCG isolates, which suggests their
potential as multidrug-resistant (MDR) phenotypes. Phylogenetic analysis showed that the two isolates
were distantly related, and the M1_S48 clinical isolate was closely related to M. bovis BCG Moscow. The
phylogenomics results imply that two different BCG strains may be circulating in South Africa. However,
it is difficult to associate the BCG vaccine strain administered and the BCG strain supplied with specific
adverse events, as BCGiosis is under-reported. This study presents background genomic information for
future surveillance and tracking of the distribution of BCGiosis-associated mycobacteria. It is also the
first
to report on the genomes of clinical BCG strains in Africa.
