The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2012
Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea.
СтатьяResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kim H J, Kwak H K, Lee J, Yun Y J, Lee J S, Lee M S, Min S Y, Park S K, Kang H S, Maeng Y H, Kim S Y, Kim S Y, Kook Y H, Kim Y R, Lee K H
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAmidohydrolasesAntitubercular AgentsBacterial ProteinsBase SequenceDNA Mutational AnalysisDrug Resistance, Multiple, BacterialExtensively Drug-Resistant TuberculosisFemaleGenotypeHumansMaleMicrobial Sensitivity TestsMiddle AgedMolecular Sequence DataMutationMycobacterium tuberculosisPhenotypePolymerase Chain ReactionPredictive Value of TestsPrognosisPyrazinamideRepublic of KoreaTuberculosis, Multidrug-Resistant