Free Content Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea

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Abstract:

BACKGROUND: Pyrazinamide (PZA), one of the most effective anti-tuberculosis drugs, becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (PZase). PZA resistance is caused mainly by the loss of enzyme activity by mutation.

OBJECTIVE: To investigate the patterns of pncA mutations in PZA-resistant mycobacteria isolated from South Korean patients.

METHODS: Mycobacterial isolates with clinically proven drug resistance were cultured to determine susceptibility to anti-tuberculosis agents. pncA mutations were recognised by sequencing and compared with the relevant wild-type DNA sequence.

RESULTS: Among 108 isolates, 102 were successfully cultured and underwent drug susceptibility testing; all were multidrug-resistant (MDR). pncA mutations were found in 86 cultured isolates (85.1%): 55 (84.6%) in MDR and 31 (86.1%) in extensively drug-resistant isolates. Substitution of a single nucleotide was most common. The most frequent mutations were a deletion that caused a frameshift at nucleotide (nt) 71, a substitution at nt 403 and a substitution at nt 11. Combined, these accounted for ∼40% of all mutations. However, 15 samples (14.9%) with defective PZase activity showed no mutation.

CONCLUSION: pncA mutation in M. tuberculosis is a major mechanism of PZA resistance in MDR isolates from patients in South Korea. The patterns of mutation might be more scattered and diverse. DNA-based diagnosis of PZA resistance has potential for the rapid detection of drug resistance.

Keywords: South Korea; amidohydrolases; anti-tuberculosis agents; multidrug resistance; mutation; pncA; tuberculosis

Document Type: Research Article

DOI: http://dx.doi.org/10.5588/ijtld.10.0739

Affiliations: 1: Jeju National University School of Medicine, Jeju, Korea 2: International Tuberculosis Research Center, Masan, Korea 3: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea 4: National Masan Hospital, Masan, Korea

Publication date: January 1, 2012

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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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