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Gene Review

inhA  -  NADH-dependent enoyl-[ACP] reductase

Mycobacterium tuberculosis H37Rv

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Disease relevance of inhA


High impact information on inhA

  • A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis and in M. bovis [1].
  • Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance [2].
  • Mutations in the inhA promoter region occurred in 25 (25.8%) of the INH-resistant isolates; 6.2% of the isolates had inhA structural gene mutations, and 10.3% had mutations in the oxyR-ahpC intergenic region (one, nucleotide -48, previously unreported) [3].
  • Sequencing of consecutive isolates identified by the National Tuberculosis Program showed 89% of isoniazid-resistant isolates could be detected by targeting just 2 codons, katG 315 and -15C-->T in the inhA promoter, while rifampin resistance will be more complex to detect, with many different mutation and insertion events in rpoB [4].

Biological context of inhA

  • The nucleotide sequences of the katG and inhA genes and the mabA-inhA promoter region were also determined [5].
  • In the case of resistance to INH, four different mutations in the katG gene were detected, Ser315-->Thr (58.0%), Ser315-->Leu (2.9%), partial deletion (5.8%) and Ile304-->Val (1.4%), while in the inhA regulatory region the only mutation was the nucleotide substitution C209T (4.3%) [6].
  • OBJECTIVES: To determine tuberculosis drug resistance among new and previously treated cases, the risk factors associated with resistance, and the mutations associated with isoniazid and rifampicin (katG, inhA and rpoB genes) resistance, and to genotype resistant strains [7].

Associations of inhA with chemical compounds

  • The sample included isoniazid (INH)-susceptible and -resistant organisms in which the katG gene and inhA locus had previously been sequenced in their entirety to identify polymorphisms [8].

Analytical, diagnostic and therapeutic context of inhA

  • The PCR products of selected regions of the katG gene, the oxyR-ahpC intergenic region, and the inhA regulatory region were analyzed utilizing the double gradient-denaturing gradient gel electrophoresis (DG-DGGE) technique and confirmed by DNA sequencing [9].


  1. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, K.S., Wilson, T., Collins, D., de Lisle, G., Jacobs, W.R. Science (1994) [Pubmed]
  2. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Hazbón, M.H., Brimacombe, M., Bobadilla del Valle, M., Cavatore, M., Guerrero, M.I., Varma-Basil, M., Billman-Jacobe, H., Lavender, C., Fyfe, J., García-García, L., León, C.I., Bose, M., Chaves, F., Murray, M., Eisenach, K.D., Sifuentes-Osornio, J., Cave, M.D., Ponce de León, A., Alland, D. Antimicrob. Agents Chemother. (2006) [Pubmed]
  3. Screening and characterization of mutations in isoniazid-resistant Mycobacterium tuberculosis isolates obtained in Brazil. Cardoso, R.F., Cooksey, R.C., Morlock, G.P., Barco, P., Cecon, L., Forestiero, F., Leite, C.Q., Sato, D.N., Shikama, M.d.e. .L., Mamizuka, E.M., Hirata, R.D., Hirata, M.H. Antimicrob. Agents Chemother. (2004) [Pubmed]
  4. Mutations prevalent among rifampin- and isoniazid-resistant Mycobacterium tuberculosis isolates from a hospital in Vietnam. Caws, M., Duy, P.M., Tho, D.Q., Lan, N.T., Hoa, D.V., Farrar, J. J. Clin. Microbiol. (2006) [Pubmed]
  5. Performance of the Genotype MTBDR Line Probe Assay for Detection of Resistance to Rifampin and Isoniazid in Strains of Mycobacterium tuberculosis with Low- and High-Level Resistance. Brossier, F., Veziris, N., Truffot-Pernot, C., Jarlier, V., Sougakoff, W. J. Clin. Microbiol. (2006) [Pubmed]
  6. Rifampin and isoniazid resistance associated mutations in Mycobacterium tuberculosis clinical isolates in Seville, Spain. Torres, M.J., Criado, A., Gónzalez, N., Palomares, J.C., Aznar, J. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. (2002) [Pubmed]
  7. Study of resistance to anti-tuberculosis drugs in five districts of Equatorial Guinea: rates, risk factors, genotyping of gene mutations and molecular epidemiology. Tudó, G., González, J., Obama, R., Rodríguez, J.M., Franco, J.R., Espasa, M., Simarro, P.R., Escaramís, G., Ascaso, C., García, A., Jiménez de Anta, M.T. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. (2004) [Pubmed]
  8. Analysis of the oxyR-ahpC region in isoniazid-resistant and -susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities. Sreevatsan, S., Pan, X., Zhang, Y., Deretic, V., Musser, J.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  9. Detection of resistance to isoniazid by denaturing gradient-gel electrophoresis DNA sequencing in Mycobacterium tuberculosis clinical isolates. Scarpellini, P., Carrera, P., Cichero, P., Gelfi, C., Gori, A., Ferrari, M., Zingale, A., Lazzarin, A. New Microbiol. (2003) [Pubmed]
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