Multiple Mycobacterium tuberculosis enzymes

Multiple Mycobacterium tuberculosis enzymes refer to the diverse set of protein catalysts essential for the survival, replication, and pathogenesis of the bacterium responsible for tuberculosis (Nature Reviews Microbiology, 2013). These enzymes are the primary targets for both first-line and second-line anti-tubercular drugs. Key pathways targeted include the biosynthesis of mycolic acids, which are critical components of the mycobacterial cell wall, as well as DNA transcription and protein synthesis (PubMed: 23435242). For example, the enzyme InhA is targeted by isoniazid to inhibit cell wall assembly (UniProt: P9WGR1), while RNA polymerase is targeted by rifampicin to halt gene expression (UniProt: P9WGY9). Other enzymes like ATP synthase and DNA gyrase are targeted by newer or second-line agents like bedaquiline and fluoroquinolones, respectively (PubChem: CID 5381; UniProt: P9WPR1). The complexity of the mycobacterial life cycle, including its ability to persist in a dormant state, necessitates the targeting of multiple enzymes to achieve complete sterilization of the infection. Inhibition of these enzymes leads to the disruption of bacterial homeostasis, eventually resulting in cell death or inhibited growth. Understanding the structural and functional characteristics of these enzymes is vital for overcoming drug resistance, which often arises from mutations in the genes encoding these targets (WHO Global Tuberculosis Report).

Other names

M. tuberculosis enzyme targetsMtb enzymesEssential Mycobacterium tuberculosis proteinsMycobacterial drug targets

Inhibition of essential bacterial enzymes involved in cell wall synthesis (e.g., InhA), nucleic acid replication (e.g., DNA gyrase), transcription (e.g., RNA polymerase), and energy metabolism (e.g., ATP synthase).