The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance

Asesh Banerjee, Michele Sugantino, James C. Sacchettini, William R. Jacobs

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2697-2704
Number of pages8
JournalMicrobiology
Volume144
Issue number10
DOIs
StatePublished - Oct 1998

Fingerprint

Mycolic Acids
Isoniazid
Operon
Mycobacterium tuberculosis
Oxidoreductases
Ethionamide
Genes
Mycobacterium bovis
Mycobacterium smegmatis
Ribosomes
Point Mutation
Dissection
Tuberculosis
Binding Sites
Escherichia coli
Phenotype

Keywords

  • Drug resistance
  • Ethionamide
  • inhA gene
  • Isoniazid
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Microbiology

Cite this

The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance. / Banerjee, Asesh; Sugantino, Michele; Sacchettini, James C.; Jacobs, William R.

In: Microbiology, Vol. 144, No. 10, 10.1998, p. 2697-2704.

Research output: Contribution to journalArticle

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