Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori

Gut Liver. 2018 Nov 15;12(6):641-647. doi: 10.5009/gnl18111.

Abstract

Background/aims: Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important.

Methods: We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing.

Results: Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (κ-value=0.990; standard error, 0.010).

Conclusions: H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.

Keywords: Clarithromycin; Helicobacter pylori; Melting array; Peptide nucleic acids.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / pharmacology*
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics
  • Helicobacter Infections / drug therapy
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / isolation & purification
  • Humans
  • Microbial Sensitivity Tests / methods
  • Peptide Nucleic Acids / analysis*
  • Point Mutation
  • Republic of Korea

Substances

  • Anti-Bacterial Agents
  • Peptide Nucleic Acids
  • Clarithromycin