Characteristic of the Mycobacterium tuberculosis genome of Beijing genotype of cluster 100-32 displaying pre-extended drug resistance

Abstract

A whole genome sequencing was performed of strain M. tuberculosis 11502 (NCBI biosamples database, access code SAMN17832565) that was assigned to the Beijing genotype subtype B0/W148 of cluster 100-32, based on the MIRU- VNTR loci (n = 24) structure, a nd t hat exhibited pre-extended d rug resistance. M. tuberculosis 11502 was resistant to isoniazid, rifampicin, ethambutol, levofloxacin, and ethionamide, which correlated with the presence of mutations in the genes: resistance to isoniazid – the mutations in the fabG1 promoter (p.-8T>C), the katG promoter (p.S315T), to ethionamide – the mutations in ethA (deletion of T at position 4 335 027 (gatgc-gagc)); to fluoroquinolones – in the gyrA gene (p.D94G); to ethambutol – in the embB gene (p.M306I); to streptomycin – in the rpsL gene (p.K43R). M. tuberculosis 11502 genome (Gen- Bank NCBI access code – CP070338) contained 4 420 561 base pairs, 4 104 genes, 4 053 CDSs (coding proteins – 3 874) and differed from reference strain M. tuberculosis H37Rv by the presence of 2 055 mutations. A slight drift of mutations towards the G+C accumulation was revealed, which indicates the importance of maintaining a high G+C content in the Mycobacterium spp.genome Strain M. tuberculosis 11502 has a higher number of mutations in comparison to previously sequenced M. tuberculosis 4860 (GenBank Access Code, NCBI: CP053092) belonging to the LAM genotype (2055 vs. 1577 mutations), which may be a consequence of a longer circulation of M. tuberculosis 11502, or some biological features providing the promutagenic effect.