Multidrug-resistant tuberculosis: a comprehensive review of pathogenesis, drug resistance, current treatment and future prospects.

Tuberculosis (TB) accounted for almost 1.2 million deaths in 2024. It remains a leading cause of mortality due to an airborne infectious bacterium, Mycobacterium tuberculosis (MTB). Despite the development of vaccines and antibiotics to cure the disease, it remains a major global problem due to the development of several ingenious pathogenic pathways. This comprehensive review introduces the mechanisms of bacterial pathogenesis against the human defence system and the development of drugs against MTB, with particular emphasis on the mechanisms of drug resistance and mutations that render them ineffective globally. There is also a discussion of the MTB lineage and the mutant types. The mechanisms of multidrug resistance and ineffective treatment regimens have driven advances in drug development and alternative therapeutics. New molecules that can potentially disarm MTB have been explored, including SQ109, GuaB2, Q203, Largazole, and Auranofin. In addition, natural compounds, bacteriophage therapy, antimicrobial peptides, and probiotics are also explored to help address the global threat posed by MTB.