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Usefulness of Mycobacterium tuberculosis genomic mutations in the genes katG and inhA for the prediction of isoniazid resistance

Authors: Dobner, P.1; Rüsch-Gerdes, S.2; Bretzel, G.3; Feldmann, K.4; Rifai, M.4; Löscher, T.1; Rinder, H.1

Source: The International Journal of Tuberculosis and Lung Disease, Volume 1, Number 4, August 1997 , pp. 365-369(5)

Publisher: International Union Against Tuberculosis and Lung Disease

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SETTING: Mutations in two genes of Mycobacterium tuberculosis, inhA and katG, are known to correlate with resistance to isoniazid (INH).

OBJECTIVE: To determine which mutation or mutations are the most predictive for INH resistance and the most frequent ones in such isolates. Further, to propose a simple and generally applicable method for their detection.

DESIGN: Codons 94 and 95 in the inhA gene and codons 315 and 463 in the katG gene were characterized in 50 INH-resistant and 12 INH-sensitive isolates from Germany and Sierra Leone.

RESULTS: Mutations in codon 315 of the katG gene were detected in 27 of the INH-resistant and none of the INH-sensitive isolates. All mutations in this codon altered an AciI restriction enzyme site. No mutations were found in the investigated codons of the inhA gene.

CONCLUSION: We propose that most INH resistances can be rapidly predicted by a simple AciI restriction enzyme digest of a polymerase chain reaction (PCR)-amplified katG fragment.

Keywords: Mycobacterium tuberculosis; inhA; isoniazid resistance; katG

Document Type: Regular Paper

Affiliations: 1: Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany 2: National Reference Center for Mycobacteria, Borstel, Germany 3: Armauer Hansen Institute, Würzburg, Germany 4: Institute for Laboratory Medicine, Central Hospital Gauting, Gauting, Germany

Publication date: August 1, 1997

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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.

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