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Gene Review

iniA  -  isoniazid inductible protein IniA

Mycobacterium tuberculosis H37Rv

 
 
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Disease relevance of iniA

  • BCG strains overexpressing M. tuberculosis iniA grew and survived longer than control strains upon exposure to inhibitory concentrations of either INH or EMB [1].
 

High impact information on iniA

  • DECAL was used to investigate the in vitro effect of the antibiotic isoniazid on M. tuberculosis, and three previously uncharacterized isoniazid-induced genes, iniA, iniB, and iniC, were identified [2].
  • The iniA gene is also induced by the antibiotic ethambutol, an agent that inhibits cell wall biosynthesis by a mechanism that is distinct from isoniazid [2].
  • Drugs designed to inhibit the iniA gene product may shorten the time required to treat tuberculosis and may help prevent the clinical emergence of drug resistance [1].
  • Additional studies showed that overexpression of M. tuberculosis iniA in BCG conferred resistance to ethidium bromide, and the deletion of iniA in M. tuberculosis resulted in increased accumulation of intracellular ethidium bromide [1].
  • Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in the iniA operon [3].
 

Biological context of iniA

References

  1. The Mycobacterium tuberculosis iniA gene is essential for activity of an efflux pump that confers drug tolerance to both isoniazid and ethambutol. Colangeli, R., Helb, D., Sridharan, S., Sun, J., Varma-Basil, M., Hazbón, M.H., Harbacheuski, R., Megjugorac, N.J., Jacobs, W.R., Holzenburg, A., Sacchettini, J.C., Alland, D. Mol. Microbiol. (2005) [Pubmed]
  2. Identification of differentially expressed mRNA in prokaryotic organisms by customized amplification libraries (DECAL): the effect of isoniazid on gene expression in Mycobacterium tuberculosis. Alland, D., Kramnik, I., Weisbrod, T.R., Otsubo, L., Cerny, R., Miller, L.P., Jacobs, W.R., Bloom, B.R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. Ramaswamy, S.V., Amin, A.G., Göksel, S., Stager, C.E., Dou, S.J., El Sahly, H., Moghazeh, S.L., Kreiswirth, B.N., Musser, J.M. Antimicrob. Agents Chemother. (2000) [Pubmed]
  4. Characterization of the Mycobacterium tuberculosis iniBAC promoter, a promoter that responds to cell wall biosynthesis inhibition. Alland, D., Steyn, A.J., Weisbrod, T., Aldrich, K., Jacobs, W.R. J. Bacteriol. (2000) [Pubmed]
 
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