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Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features?

P Escalante1, R McKean-Cowdin, S V Ramaswamy

  • 1Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. escalante.patricio@mayo.edu

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
|March 5, 2013
PubMed
Abstract

Insights

Isoniazid-resistant tuberculosis (TB) with non-katG mutations shows faster treatment response. However, katG mutations in Mycobacterium tuberculosis are linked to localized lung disease. This impacts clinical TB management.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Isoniazid-resistant (INHr) Mycobacterium tuberculosis often harbors katG mutations, a known virulence factor in animal models.
  • The impact of katG mutations versus other mutations on human tuberculosis (TB) clinical presentation remains unclear.

Purpose of the Study:

  • To investigate associations between isoniazid-resistance conferring mutations in Mycobacterium tuberculosis and distinct clinical features of tuberculosis.
  • To compare clinical characteristics of patients with INHr TB and pan-susceptible (PS) TB.

Main Methods:

  • Retrospective case-control study design.
  • DNA sequencing used to identify INHr-conferring mutations, including katG-S315T and inhA-C(-)15T.
  • Clinical data from 29 INHr TB cases and 50 PS controls were analyzed.

Main Results:

  • No statistically significant differences in overall disease characteristics between INHr and PS TB cases.
  • Patients with non-katG INHr mutants showed a higher rate of sputum culture conversion at 1 month (aOR 4.4).
  • Patients with katG mutants were associated with a higher rate of unilateral disease (aOR 4.7).

Conclusions:

  • Most INHr TB cases with non-katG mutations exhibit a faster treatment response.
  • Cases with katG mutations are more frequently associated with localized lung involvement in tuberculosis.

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