Screening mutations in drug-resistant Mycobacterium tuberculosis strains in Yunnan, China

J Infect Public Health. 2017 Sep-Oct;10(5):630-636. doi: 10.1016/j.jiph.2017.04.008. Epub 2017 Jun 13.

Abstract

Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB), is a serious medical and societal problem in China. The purpose of this study was to evaluate the mutation characteristics of drug-resistant Mycobacterium tuberculosis (M. tuberculosis) isolates in Yunnan, China. Drug susceptibility testing (DST) was performed in 523 clinical M. tuberculosis isolates. Six drug resistance genes (katG, inhA, rpoB, rpsL, embB, and pncA) were selected to screen for mutations. In total, 54 clinical M. tuberculosis strains were identified as drug-resistant by DST, including 18 single drug-resistant (SDR) strains and 36 multidrug-resistant (MDR) strains. Twenty-four types of mutations in five genes (excluding the inhA gene) were screened in forty-one strains. Six novel mutations were identified in this study, including three missense mutations (p.S302R in katG, p.D78G in embB, and p.M1I in pncA), two frameshift mutations (408 ins A and 538-580 del in pncA), and one mutation in a control region (-6 C>T located upstream of rpsL). The mutation frequencies in the hotspot mutation regions in the katG, rpoB, rpsL, embB, and pncA genes were 92.5%, 44.4%, 54.2%, 52.6%, and 37.5%, respectively. The mutation spectra and frequencies seemed somewhat unique in the Yunnan DR-TB strains.

Keywords: Drug resistance genes; Mutation frequency; Mycobacterium tuberculosis; Novel mutation.

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • China
  • DNA Mutational Analysis
  • DNA, Bacterial
  • Drug Resistance, Bacterial / genetics
  • Evolution, Molecular
  • Gene Frequency
  • Genes, Bacterial
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mutation*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Protein Conformation
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • DNA, Bacterial