The Sound of Evolution
Isoniazid
Mechanism of action:
Isoniazid is an isonicotinic acid hydrazide derivative. After entering Mycobacterium tuberculosis, it is converted by the bacterial peroxidase/catalase KatG into an active intermediate. This active intermediate inhibits enzymes such as InhA and KasA, thereby blocking the synthesis of mycolic acid. Mycolic acid is a key lipid component of the mycobacterial cell wall and is essential for maintaining cell wall integrity and acid-fastness. Inhibition of its synthesis leads to disruption of the bacterial cell wall and ultimately bacterial death.
Reference(s):
1. Pym AS et al. (2001). Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol Microbiol.
2. Heym B et al. (1995). Missense mutations in the catalase-peroxidase gene, katG, are associated with isoniazid resistance in Mycobacterium tuberculosis. Mol Microbiol.
3. Wilson TM et al. (1995). Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Mol Microbiol.