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Correlation between pyrazinamide activity and pncA mutations in Mycobacterium tuberculosis isolates in Taiwan.

ABSTRACT: A total of 76 clinical Mycobacterium tuberculosis isolates from Taiwan were tested for pyrazinamidase activity, pyrazinamide susceptibility, and pncA mutations. Frequency of resistance to PZA rose with increases in resistance to first-line drugs. Of 17 pyrazinamide-resistant strains, 7 (3 of which had not been previously described) possessed mutations in the pncA gene.

SUBMITTER: Huang TS

PROVIDER: S-EPMC253789 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature

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Correlation between pyrazinamide activity and pncA mutations in Mycobacterium tuberculosis isolates in Taiwan.

Huang Tsi-Shu TS Lee Susan Shin-Jung SS Tu Hui-Zin HZ Huang Wen-Kuei WK Chen Yao-Shen YS Huang Chung-Kai CK Wann Shue-Ren SR Lin Hsi-Hsun HH Liu Yung-Ching YC

Antimicrobial agents and chemotherapy 20031101 11

A total of 76 clinical Mycobacterium tuberculosis isolates from Taiwan were tested for pyrazinamidase activity, pyrazinamide susceptibility, and pncA mutations. Frequency of resistance to PZA rose with increases in resistance to first-line drugs. Of 17 pyrazinamide-resistant strains, 7 (3 of which had not been previously described) possessed mutations in the pncA gene. ...[more]

PMID: 14576145

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Association between pncA gene mutations, pyrazinamidase activity, and pyrazinamide susceptibility testing in Mycobacterium tuberculosis.

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Non-pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

Project description:Pyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB). pncA gene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDRPZA-S TB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-type pncA gene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy: panD or rpsA mutations identified by whole-genome sequencing (WGS) (n = 7), heteroresistance (n = 8), and mixed populations with Mycobacterium avium (n = 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-R clinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymous pncA mutation (Thr87Met), whereas a nonsynonymous rpsA mutation was found in 17 isolates. None of these isolates carried a nonsynonymous panD mutation, while all 15 of the MDRPZA-R isolates harbored a nonsynonymous pncA mutation. Our findings indicate that it is necessary to consider the occurrence of panD mutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymous rpsA mutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role of rpsA in PZA resistance.

| S-EPMC5442549 | biostudies-literature

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