The mabA Gene From the inhA Operon of Mycobacterium Tuberculosis Encodes a 3-ketoacyl Reductase That Fails to Confer Isoniazid Resistance

Microbiology. 1998 Oct;144 ( Pt 10):2697-704. doi: 10.1099/00221287-144-10-2697.

Abstract

A target of the anti-tuberculosis drugs isoniazid (INH) and ethionamide (ETH) has been shown to be an enoyl reductase, encoded by the inhA gene. The mabA (mycolic acid biosynthesis A) gene is located immediately upstream of inhA in Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium smegmatis. The MabA protein from M. tuberculosis was expressed in Escherichia coli and shown to have 3-ketoacyl reductase activity, consistent with a role in mycolic acid biosynthesis. In M. smegmatis, inhA and mabA are independently transcribed, but in M. tuberculosis and M. bovis BCG, mabA and inhA constitute a single operon. Several INH-ETH-resistant M. tuberculosis clinical isolates contain point mutations in the ribosome-binding site of mabA in the mabA-inhA operon. However, genetic dissection of this operon reveals that the INH-ETH-resistance phenotype is encoded only by inhA, and not by mabA.

Publication types

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

MeSH terms

  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase
  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Sequence
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins
  • Base Sequence
  • Cloning, Molecular
  • Conserved Sequence
  • Drug Resistance, Microbial / genetics
  • Ethionamide / pharmacology
  • Genetic Vectors
  • Isoniazid / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics*
  • Operon / genetics
  • Oxidoreductases / genetics*
  • Phenotype
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Oxidoreductases
  • Alcohol Oxidoreductases
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase
  • InhA protein, Mycobacterium
  • Ethionamide
  • Isoniazid

Associated data

  • GENBANK/U66800
  • GENBANK/U66801