Development and Validation of a Clinical Laboratory Improvement Amendments-Compliant Multiplex Real-Time PCR Assay for Detection of mcr Genes

Microb Drug Resist. 2019 Sep;25(7):991-996. doi: 10.1089/mdr.2018.0417. Epub 2019 Apr 3.

Abstract

Increased use of colistin in both human and veterinary medicine has led to the emergence of plasmid-mediated colistin resistance (mcr genes). In this study, we report the development of a real-time PCR assay using TaqMan probe-based chemistry for detection of mcr genes from bacterial isolates. Positive control isolates harboring mcr-1 and mcr-2 yielded exponential amplification curves with the assay, and the amplification efficiency was 98% and 96% for mcr-1 and mcr-2, respectively. Each target gene could be reproducibly detected from a sample containing 103 cfu/mL of mcr-harboring bacteria, and there was no cross-reactivity with DNA extracted from several multidrug-resistant bacteria harboring other resistance genes, but lacking mcr genes. Both sensitivity and specificity of the mcr real-time PCR assay were 100% in a method validation performed with a set of 25 previously well-characterized bacterial isolates containing mcr-positive and -negative bacteria. This newly developed assay is a rapid and sensitive tool for detecting emerging mcr genes in cultured bacterial isolates. The assay was successfully validated according to quality standards of the Clinical Laboratory Improvement Amendments (CLIA).

Keywords: Taq-man; colistin resistance; mcr; mcr variants; multiplex; real-time PCR.

MeSH terms

  • Bacteria / genetics*
  • Colistin / metabolism*
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Genes, Bacterial / genetics*
  • Microbial Sensitivity Tests / methods
  • Multiplex Polymerase Chain Reaction / methods*
  • Plasmids / genetics
  • Real-Time Polymerase Chain Reaction / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Colistin