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Toxin-Antitoxin (TA) systems are highly conserved genetic elements in the Mycobacterium tuberculosis complex, playing a critical role in bacterial survival, stress response, and persistence. Small variations in sequence composition can lead to species-specific functional differences, potentially influencing host adaptation, antibiotic tolerance, and virulence strategies. In this study, a comparative analysis of TA systems in M. tuberculosis and M. bovis was conducted using BLAST NCBI, and SnapGene 5.3.1. A main mutation was identified at nucleotide 719 of the vapC3 gene in M. bovis isolates. While vapC3 in M. tuberculosis consists of 137 amino acids, a nucleotide deletion in M. bovis resulted in a truncated protein of only 109 amino acids in the primary sequence, significantly altering its structure. These findings suggest potential differences in the translation and function of vapC3 between the two species. Molecular docking simulations were conducted using HADDOCK 2.4 to assess the functional implications of vapC3 mutations. The analysis revealed that VapBC3 in M. bovis exhibits a more stable interaction than in M. tuberculosis, which could be crucial in understanding species-specific toxin-antitoxin system functionality. Future studies should focus on the impact of this mutation on VapC3-mediated stress response, experimental validation and therapeutic applications targeting VapBC3-mediated bacterial survival pathways.
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Shafipour et al. (2025) studied this question.
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