Mutation in pncA is a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis

High Resolution Melting Curve Analysis for Rapid Detection of Pyrazinamide Resistance in <i>Mycobacterium tuberculosis</i> Clinical Isolates

“…Some of these studies have reported this correlation to be inconsistent, ranging between 41% and 80% [25]- [31], whereas other studies showed higher correlation ranging from 91% -97% [15] [17] [32] [33] [34]. In the current study, based on sequencing results, a correlation of 0.67 (significant at p-value < 0.05) between phenotypic resistance to PZA and pncA mutation was observed, this is comparable to majority of the previous studies, more especially to the study that was conducted in South Africa by Bishop et al, in which a correlation of 67% was also reported [35].…”

Characterization ofpncAMutations of Pyrazinamide-ResistantMycobacterium tuberculosisin Korea

“…Mutation of the pncA gene was suggested as the major mechanism of PZA resistance. Several subsequent studies including 20-40 PZAresistant M. tuberculosis isolates from different countries confirmed the close correlation between pncA mutation and PZA resistance (72-97%) (17)(18)(19)(20)(21)(22)(23). These observations raised the possibility of utilizing DNA-based methods as an alternative PZA susceptibility test.…”

“…More than 200 PZA-susceptible M. tuberculosis strains failed to show any mutations of the gene including silent substitutions (18)(19)(20)23). In contrast, diverse mutations at various sites of the pncA gene were identified in PZA-resistant strains and the frequencies of mutation varied among studies (75-100%) (17)(18)(19)(20)(21)(22)(23). In this study of Korean isolates, the frequency of pncA mutation appeared to be very high (97%) in PZA-resistant M. tuberculosis.…”

Role of Metal Ions on the Activity of Mycobacterium tuberculosis Pyrazinamidase

“…Analysis of the CD data for secondary structure determination was carried out using the CDSSTR secondary structure fitting program (basis set 7) 23,24 that is available online at the Dichroweb server (http://www.cryst.bbk.ac.uk/cdweb). 25 Metal ion contents.…”

“…Because of its role in triggering the bactericidal activity of PZA, defective PZAse is often found in Mycobacterium tuberculosis PZA-resistant strains with mutations in the pncA gene that encodes PZAse. 1,[4][5][6][7][8][9][10] Important molecular characteristics of M. tuberculosis PZAse have been elucidated from crystallized homologous hydrolases such as N-Carbamoylsarcosine amidohydrolase (CHSase) from Arthrobacter (26% identical), 11 PZAse from Pyrococcus horikoshii (37% identical), 12 and PZAse from Acinetobacter baumanii (37% identical) 13 as well as the recently crystallized structure of M. tuberculosis pyrazinamidase 14 and a theoretical analysis of a modeled structure. 15 According to these studies, the catalytic cavity comprises an active site (D8, A134, and C138) and a metal-binding site (D49, H51, and H71).…”