Can mycobacterial katG genetic changes in isoniazid-resistant tuberculosis influence human disease features?
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.
Document Type: Research Article
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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