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.
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.
Authors: Kathy Williams; Austin Minkowski; Opokua Amoabeng; Charles A Peloquin; Dinesh Taylor; Koen Andries; Robert S Wallis; Khisimuzi E Mdluli; Eric L Nuermberger Journal: Antimicrob Agents Chemother Date: 2012-04-02 Impact factor: 5.191
Authors: Ekaterina V Kurbatova; Joseph S Cavanaugh; Tracy Dalton; Eleanor S Click; J Peter Cegielski Journal: Clin Infect Dis Date: 2013-07-09 Impact factor: 9.079
Authors: Ekaterina V Kurbatova; Tracy Dalton; Julia Ershova; Thelma Tupasi; Janice Campos Caoili; Martie Van Der Walt; Charlotte Kvasnovsky; Martin Yagui; Jaime Bayona; Carmen Contreras; Vaira Leimane; Laura E Via; HeeJin Kim; Somsak Akksilp; Boris Y Kazennyy; Grigory V Volchenkov; Ruwen Jou; Kai Kliiman; Olga V Demikhova; J Peter Cegielski Journal: Emerg Infect Dis Date: 2015-06 Impact factor: 6.883
Authors: Michael G Whitfield; Heidi M Soeters; Robin M Warren; Talita York; Samantha L Sampson; Elizabeth M Streicher; Paul D van Helden; Annelies van Rie Journal: PLoS One Date: 2015-07-28 Impact factor: 3.240