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: 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.

Flea-borne Mycobacterium and Mycoplasma in Small Ruminants on the Northern West Coast of Egypt

“…The sequence of Mycobacterium bovis got from this study was 90.2-100%, and Mycoplasma was identical from 82.8-100% to previously submitted sequences in GenBank (Borgers et al 2019;Modipane et al 2019;Oliveira et al 2022). The divergence table of the 16S rRNA gene showed a divergence from 0.0 to 7.7 for Mycobacterium and from 0.0 to 17.3 for Mycoplasma between submitted and other isolates preserved in the GenBank database (Supplementary Tables 1, 2).…”

“…According to phylogenetic tree analysis, the present isolation of Mycobacterium bovis (ON076426) is present in one clade with seven preserved strains in GenBank with 100% identity and the highest bootstrap value. Of the identical strains were CP039850 and CP039851 recorded from Belgium (Borgers et al 2019), CP040832 (Brazil) (Oliveira et al 2022), and CP033311 (South Africa) (Modipane et al 2019). They were isolated respectively from Tapirus terrestris, Homo sapiens, animal organs, and fleas.…”

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

“…Adverse events following immunization with BCG are considered underreported since assays to confirm isolates as BCG are still relatively rare. Moreover, based on the routine laboratory diagnostics and even molecular techniques, it is difficult to associate the clinical BCG isolates with the particular vaccine lot administered [15][16][17][18][19][20]. Therefore, the contribution of BCG genomic heterogeneity to the viability and residual virulence of vaccine populations in vivo remains unclear in terms of the development of BCG-related disease that otherwise can be associated with immune responses and human genetics.…”

“…The attenuated BCG vaccines are believed safe and effective mainly to prevent the most severe meningitis and miliary forms of childhood TB associated with high mortality in infants and young children, especially in high TB-burden countries [1,2]. However, adverse events following immunization with BCG in 1-10% of vaccinees are likely to be substantially underreported since assays to confirm isolates as BCG are still relatively rare [15][16][17][18][19][20] despite the advent of molecular techniques and commercially available kits for BCG identification [21]. In Russia, the estimated frequency of complications per 100,000 BCGimmunized decreased from 35.3 in 2005 to 11.2 in 2013 [22].…”

“…During the last decades, the whole-genome sequencing (WGS) was applied to assess the genome stability of BCG vaccine strains from different culture collections and to evaluate the impact of minor sequence variations occurring in seed and commercial lots on the efficacy of BCG-vaccines used in different countries [ 30 – 34 ]. Recently, sequence variations were identified in clinical isolates from two infants with BCG-induced disease compared with the sub-cultured M. bovis BCG Moscow strain (Serum Institute of India, India) in South Africa [ 15 ].…”