Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea
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.
Document Type: Research Article
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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