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Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa

Authors: Bishop K., S.1; Blumberg, L.2; Trollip A., P.2; Smith A., N.1; Roux, L.3; York D., F.1; Kiepiela, P.1

Source: The International Journal of Tuberculosis and Lung Disease, Volume 5, Number 10, October 2001 , pp. 952-957(6)

Publisher: International Union Against Tuberculosis and Lung Disease

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Abstract:

SETTING: The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa.

OBJECTIVE: To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method.

DESIGN: The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined.

RESULTS: All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZA-susceptible pattern was obtained on BACTEC and the wild type pncA sequence was present.

CONCLUSION: Sequencing is an effective means to identify mutations in the pncA gene in M. tuberculosis and therefore resistance to PZA. The fact that some PZA-resistant M. tuberculosis isolates lack mutations in the pncA gene suggests that alternative mechanisms for drug resistance exist. In PZase negative strains with no genetic changes which are resistant to 100 μg/ml and susceptible to 300 μg/ml, 300 μg/ml may be a more reliable breakpoint.

Keywords: M. tuberculosis; pncA gene mutations; pyrazinamide resistance

Document Type: Regular Paper

Affiliations: 1: Department of Virology, Faculty of Medicine, University of Natal, Durban, KwaZulu-Natal, South Africa 2: SAIMR Tuberculosis Reference Laboratory, Gauteng, South Africa 3: Department of Medical Microbiology, Faculty of Medicine, University of Natal, Durban, KwaZulu-Natal, South Africa

Publication date: October 1, 2001

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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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