inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa?

Int J Tuberc Lung Dis. 2011 Mar;15(3):344-51.


Setting: Western Cape and Eastern Cape Provinces, South Africa.

Objective: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene.

Design: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis.

Results: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%).

Conclusions: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the GenoType® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / epidemiology
  • Extensively Drug-Resistant Tuberculosis / genetics
  • Genotype
  • Humans
  • Molecular Probe Techniques
  • Mutation
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Oxidoreductases / genetics*
  • Pharmacogenetics
  • Promoter Regions, Genetic
  • South Africa / epidemiology


  • Antitubercular Agents
  • Bacterial Proteins
  • Oxidoreductases
  • InhA protein, Mycobacterium