inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis

Science. 1994 Jan 14;263(5144):227-30. doi: 10.1126/science.8284673.


Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. 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. The wild-type inhA gene also conferred INH and ETH resistance when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG. The InhA protein shows significant sequence conservation with the Escherichia coli enzyme EnvM, and cell-free assays indicate that it may be involved in mycolic acid biosynthesis. These results suggest that InhA is likely a primary target of action for INH and ETH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Base Sequence
  • Cloning, Molecular
  • Drug Resistance, Microbial / genetics*
  • Ethionamide / metabolism
  • Ethionamide / pharmacology*
  • Genes, Bacterial*
  • Isoniazid / metabolism
  • Isoniazid / pharmacology*
  • Molecular Sequence Data
  • Mutation
  • Mycobacterium / drug effects
  • Mycobacterium / genetics
  • Mycobacterium bovis / drug effects
  • Mycobacterium bovis / genetics
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / metabolism
  • Mycolic Acids / metabolism
  • Open Reading Frames
  • Oxidoreductases*
  • Sequence Alignment


  • Bacterial Proteins
  • Mycolic Acids
  • Oxidoreductases
  • InhA protein, Mycobacterium
  • Ethionamide
  • Isoniazid

Associated data

  • GENBANK/U02492
  • GENBANK/U02530