Isoniazid is a bactericidal and bacteriostatic against Mycobacterium tuberculosis, the causal agent of tuberculosis.
| Mechanism of Action | Isoniazid itself is not toxic to the bacterial cell, but acts as a prodrug and is activated by the Mycobacterial enzyme KatG, a catalase-peroxidase. This enzyme prevents the formation of unstable oxygen radicals. Once activated, isoniazid binds to and inactivates InhA, an enoyl-reductase involved in mycolic acid synthesis. The inhibition of cell wall lipid synthesis, depletion of nucleic acid pools and metabolic depression contribute to the potency and selectivity. |
| Spectrum | Isoniazid targets Mycoplasma species including M. tuberculosis, M. bovis, and M. kansasii. |
| Microbiology Applications | A missense mutation within the Mycobacterial inhA gene was shown to confer resistance to Isoniazid in M. smegmatis and M. bovis. The wild-type inhA gene also conferred resistance when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG. (Banerjee et al, 1994). |
| References | Banerjee A et al (1994) InhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. 263(5144):227-230 Johnsson K (1994) Studies on the mechanism of action of Isoniazid and Ethionamide in the chemotherapy of tuberculosis. Amer. Chem. Soc. Vol 5009-010 |
| MIC | Mycobacteria| ? － ?| 1084| Mycobacterium aurum| >256 － ?| 1629| Mycobacterium aurum (ATCC 23366)| 0.06 － ?| 1084| Mycobacterium aurum (Pasteur Institute 104482)| 2 － ?| 346| Mycobacterium avium| ? － ?| 301| Mycobacterium avium (ATCC 19421)| 100 － ?| 168| Mycobacterium avium (NIHJ 1605)| 1 － ?| 394| Mycobacterium bovis (ATCC 19210)| 0.25 － ?| 1084| Mycobacterium bovis (BCG + kas(A))| 0.07 － ?| 415| Mycobacterium bovis (BCG + kas(AB))| 0.05 － ?| 415| Mycobacterium bovis (BCG + kas(B))| 0.05 － ?| 415| Mycobacterium bovis (BCG)| 0.06 － ?| 415| Mycobacterium chelonae (ATCC 14472)| >32 － ?| 1084| Mycobacterium fortuitum| 0.25 － ?| 1629| Mycobacterium fortuitum (ATCC 6841)| 0.5 － ?| 346| Mycobacterium fortuitum (ATCC 6841)| 0.5 － ?| 226| Mycobacterium fortuitum (ATCC 6841)| 2 － ?| 1084| Mycobacterium fortuitum (clinical isolate)| 2 － ?| 1084| Mycobacterium gordonae| 8 － ?| 1084| Mycobacterium intracellulare| ? － ?| 301| Mycobacterium intracellulare (ATCC 1954 E-3)| 8 － ?| 394| Mycobacterium kansasii (ATCC 12478)| 2 － ?| 394| Mycobacterium kansasii (clinical isolate)| 4 － ?| 1084| Mycobacterium paratuberculosis (ATCC 27294 + H38Rv + isoniazid-susceptible + rifampin-su)| 0.025 － 0.05| 458| Mycobacterium phlei| 2 － ?| 1084| Mycobacterium phlei| 4 － ?| 992| Mycobacterium phlei (ATCC 11758)| 2 － ?| 346| Mycobacterium scrofulaceum (ATCC 19981)| 0.5 － ?| 1084| Mycobacterium scrofulaceum (clinical isolate)| 2 － ?| 1084| Mycobacterium smegmatis (ATCC 14468)| 2 － ?| 346| Mycobacterium smegmatis (ATCC 14468)| 8 － ?| 1084| Mycobacterium smegmatis (mc155)| 2.5 － ?| 720| Mycobacterium smegmatis (mc2163)| 2 － ?| 992| Mycobacterium smegmatis (NJS30A)| 2.5 － ?| 720| Mycobacterium smegmatis (NJS30C)| 2.5 － ?| 720| Mycobacterium smegmatis (NJS31)| 2.5 － ?| 720| Mycobacterium tuberculosis| 0.06 － 64| 335| Mycobacterium tuberculosis| ? － ?| 1084| Mycobacterium tuberculosis| ? － ?| 1084| Mycobacterium tuberculosis| 0.02 － 0.06| 998| Mycobacterium tuberculosis| 0.03 － ?| 1528| Mycobacterium tuberculosis| 0.06 － 0.48| 254| Mycobacterium tuberculosis| 0.06 － ?| 993| Mycobacterium tuberculosis| 50 － ?| 1013| Mycobacterium tuberculosis| 20000 － ?| 1308| Mycobacterium tuberculosis (14d)| 2.2 － ?| 690| Mycobacterium tuberculosis (180)| 0.05 － ?| 641| Mycobacterium tuberculosis (190)| 16 － ?| 641| Mycobacterium tuberculosis (210)| 0.05 － ?| 720| Mycobacterium tuberculosis (331)| 0.05 － ?| 641| Mycobacterium tuberculosis (7d)| 1.4 － ?| 690| Mycobacterium tuberculosis (ATCC 25177 + H37Ra)| 0.1 － ?| 1334| Mycobacterium tuberculosis (ATCC 25180)| 10 － ?| 1577| Mycobacterium tuberculosis (ATCC 27294 + isoniazid-resistant)| 30 － ?| 254| Mycobacterium tuberculosis (ATCC 27294)| 0.015 － ?| 1128| Mycobacterium tuberculosis (ATCC 27294)| 0.025 － 0.2| 644| Mycobacterium tuberculosis (ATCC 27294)| 0.03 － ?| 720| Mycobacterium tuberculosis (ATCC 27294)| 0.04 － ?| 254| Mycobacterium tuberculosis (ATCC 27294)| 0.5 － ?| 641| Mycobacterium tuberculosis (ATCC 35801 + Erdman)| 1.6 － ?| 1007| Mycobacterium tuberculosis (ATCC 35801)| 0.06 － ?| 993| Mycobacterium tuberculosis (BACTEC 460 + H37Ra)| 0.05 － ?| 997| Mycobacterium tuberculosis (BACTEC 460 + H37Ragfp)| 0.0125 － 0.05| 997| Mycobacterium tuberculosis (Beijing)| 0.125 － ?| 993| Mycobacterium tuberculosis (GFPMA H37Ragfp)| 0.0125 － 0.05| 997| Mycobacterium tuberculosis (H37Ra)| 10 － ?| 1007| Mycobacterium tuberculosis (H37Rv + isoniazid-resistant)| >1 － ?| 1332| Mycobacterium tuberculosis (H37RV)| 0.03 － ?| 1095| Mycobacterium tuberculosis (H37Rv)| 0.06 － ?| 1332| Mycobacterium tuberculosis (H37Rv)| 0.1 － ?| 1547| Mycobacterium tuberculosis (H37Rv)| 0.5 － ?| 1158| Mycobacterium tuberculosis (H37Rv)| 10 － ?| 1007| Mycobacterium tuberculosis (isoniazid-resistant + rifampicin-resistant)| 1 － 64| 335| Mycobacterium tuberculosis (isoniazid-resistant)| >8 － ?| 993| Mycobacterium tuberculosis (isoniazid-resistant)| 50 － ?| 168| Mycobacterium tuberculosis (levofloxacin-resistant)| ? － ?| 301| Mycobacterium tuberculosis (levofloxacin-susceptible)| ? － ?| 301| Mycobacterium tuberculosis (multidrug drug resistant)| 2 － ?| 993| Mycobacterium tuberculosis (multidrug drug resistant)| 4 － ?| 993| Mycobacterium tuberculosis (multidrug-resistant)| ? － ?| 301| Mycobacterium tuberculosis (multidrug-resistant)| 1.33 － ?| 993| Mycobacterium tuberculosis (non-multidrug-resistant)| ? － ?| 301| Mycobacterium tuberculosis (pH 5.5)| 0.16 － ?| 254| Mycobacterium tuberculosis (pH 6.8)| 0.04 － ?| 254| Mycobacterium tuberculosis (quinolone-resistant)| 0.03 － ?| 993| Mycobacterium tuberculosis (streptomycin-resistant)| 0.125 － ?| 993| Mycobacterium vaccae (ATCC 15483)| 0.5 － ?| 1084| Mycobacterium xenopi (ATCC 19970)| 0.125 － ?| 1084| Mycobacterium xenopi (clinical isolate)| 2 － ?| 1084| |