WGS on environmental stress treated Mycobacterium smegmatis

Tuberculosis remains among the most prevalent infectious diseases globally, with approximately 10 million active cases, 1.7 billion latent infections, and 1.5 million deaths annually. The enduring success of Mycobacterium tuberculosis as a pathogen is largely attributable to its capacity for long-term persistence within macrophages and its limited susceptibility to antibiotic treatment. The molecular mechanisms underlying stress adaptation and mutability remain largely unresolved in Mycobacteria. To explore the relationship between stress responses, genetic variability, and their relevance to mycobacterial survival strategies, we assessed the impact of host-associated stressors on genome integrity using Mycobacterium smegmatis, a non-pathogenic surrogate for clinically important species. Whole-genome sequencing revealed that prolonged exposure to nutrient deprivation, anaerobic conditions, sodium nitrite, or hydrogen peroxide produced negligible increases in mutation frequency. We also examined the effects of antimicrobial agents such as streptomycin, cycloserine, and 5-fluorouracil. The influence of these compounds on mycobacterial cellular homeostasis and genome integrity is particularly relevant from the perspective of resistance. Our findings demonstrate that extended treatment with these factors does not significantly compromise the genomic stability of M. smegmatis, underscoring the robustness of mycobacterial genomes against both environmental and pharmacological stress.