A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis

Sci Rep. 2019 Mar 14;9(1):4425. doi: 10.1038/s41598-019-39339-3.

Abstract

Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of Mycobacterium tuberculosis complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes: rpoB, katG, inhA, ahpC, embB, rpsL, gyrA, rrs and eis. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDRplus and MTBDRsl tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDRplus test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDRsl test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / therapeutic use*
  • Bacterial Proteins / genetics*
  • DNA, Bacterial / analysis
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Extensively Drug-Resistant Tuberculosis / drug therapy
  • Extensively Drug-Resistant Tuberculosis / microbiology*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Oligonucleotide Array Sequence Analysis / methods*
  • Sequence Analysis, DNA / methods*

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • DNA, Bacterial