Pyrazinamide resistance among multidrug-resistant tuberculosis clinical isolates in a national referral center of China and its correlations with pncA, rpsA, and panD gene mutations

Diagn Microbiol Infect Dis. 2016 Mar;84(3):207-11. doi: 10.1016/j.diagmicrobio.2015.10.017. Epub 2015 Oct 28.

Abstract

Our study was aimed to identify the phenotypic and genotypic pyrazinamide (PZA) resistance features among multidrug-resistant (MDR) isolates in a national tuberculosis (TB) referral center of China. PZA susceptibility test was performed for a total of 142 MDR-TB clinical isolates using the MGIT 960 PZA kits, and the pncA, rpsA, and panD genes were sequenced. Extensively drug-resistant (XDR) and pre-XDR strains had higher PZA resistance rate than that of MDR strains which were still sensitive to fluoroquinolone and aminoglycoside (42.9%, 24/56) (χ(2)=8.922, P=0.012). No panD mutation was detected among the PZA resistant strains with wild-type pncA and rpsA genes. Our study indicates that PZA-resistant frequency increases with TB drug resistance level; pncA, rpsA, and panD mutations had strong, low, and no correlation with PZA resistance, and rapid molecular assay will facilitate the timely identification of the PZA-sensitive MDR-TB.

Keywords: Pyrazinamide; Resistance; Tuberculosis; pncA; rpsA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Substitution
  • Antitubercular Agents / pharmacology
  • China / epidemiology
  • Codon
  • Drug Resistance, Bacterial*
  • Female
  • Genes, Bacterial*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Open Reading Frames
  • Promoter Regions, Genetic
  • Pyrazinamide / pharmacology*
  • Sequence Analysis, DNA
  • Tuberculosis, Multidrug-Resistant / epidemiology*
  • Tuberculosis, Multidrug-Resistant / microbiology*
  • Young Adult

Substances

  • Antitubercular Agents
  • Codon
  • Pyrazinamide