Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, 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.
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: 2001-10-01
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