Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDR sl Assays

Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02169-16. doi: 10.1128/AAC.02169-16. Print 2017 Apr.

Abstract

In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

Keywords: Hain GenoType MTBDRsl; Mycobacterium tuberculosis; fluoroquinolones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Biological Assay
  • DNA Gyrase / genetics*
  • DNA Gyrase / metabolism
  • Drug Resistance, Multiple, Bacterial / genetics*
  • False Positive Reactions
  • Fluoroquinolones / pharmacology*
  • Gene Expression
  • Humans
  • Mutation*
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Oligonucleotide Probes / chemistry
  • Oligonucleotide Probes / metabolism
  • Phylogeny
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Fluoroquinolones
  • Oligonucleotide Probes
  • DNA Gyrase