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

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Abstract:

BACKGROUND: Isoniazid-resistant (INHr) Mycobacterium tuberculosis isolates often have katG mutations, and katG is a virulence factor in animal models. It is unclear if katG mutations or other mutations influence the characteristics of human disease.

OBJECTIVE: To determine if the presence of INHr-conferring mutations were associated with distinct clinical features of tuberculosis (TB).

METHODS: In a retrospective case-control study, INHr-conferring mutations were determined by DNA sequencing. We examined associations between clinical characteristics in patients with INHr M. tuberculosis (stratified by groups of relevant INHr-conferring mutations, including katG-S315T and inhA-C(−)15T mutations) and pan-susceptible (PS) isolates.

RESULTS: Twenty-nine INHr TB cases and 50 PS controls were evaluated. Disease characteristics were not statistically different between INHr and PS cases. However, patients infected with non-katG mutants were associated with a higher rate of sputum culture conversion at 1 month after adjustment for relevant covariates (adjusted OR [aOR] 4.4, 95%CI 1.1–23.6, P = 0.04). Patients infected with katG mutants were associated with a higher rate of unilateral disease (aOR 4.7, 95%CI 1.0–34.3, P = 0.05).

CONCLUSIONS: Most INHr TB cases with non-katG mutations have disease associated with faster response to treatment, and most cases with katG mutants have localized lung involvement.

Keywords: Mycobacterium tuberculosis; katG protein; resistance; virulence

Document Type: Research Article

DOI: http://dx.doi.org/10.5588/ijtld.12.0380

Affiliations: 1: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA 2: Departments of Preventive Medicine and Medicine, University of Southern California, Health Sciences Campus, Los Angeles, California, USA 3: Department of Pathology, Baylor College of Medicine, Houston, Texas, USA 4: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA 5: Department of Pathology and Genomic Medicine, Methodist Hospital Research Institute, Houston, Texas, USA 6: Division of Infectious Diseases, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, California, USA

Publication date: May 1, 2013

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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