Phylogenomic and epidemiological insights into two clinical Mycobacterium bovis BCG strains circulating in South Africa

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 Mycobacterium bovis BCG were 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 conclusion Genetic variations between the clinical strains and the reference BCG Copenhagen were identified. The clinical strains shared only one mutation in a secretion protein. We identified mutations in various antibiotic resistance genes in the BCG isolates, which suggest their potential as 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. Our phylogenomics results imply that two different BCG strains may be circulating in South Africa. However, it is difficult to associate the administered BCG vaccine strain and the supplied BCG strain 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.