Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance

J Med Microbiol. 2019 Apr;68(4):566-573. doi: 10.1099/jmm.0.000944. Epub 2019 Feb 6.

Abstract

Purpose: We aimed to investigate the presence of three recently identified point mutations (A2115G, G2141A and A2144T) of the 23 S rRNA gene and compare them with the three most frequently encountered point mutations (A2142G, A2142C and A2143G) in Helicobacter pylori strains in Turkey.

Methodology: A total of 63 patients (mean 47.08±12.27) were included. The E-test method (for clarithromycin) was used for the clarithromycin antimicrobial susceptibility test of isolated H. pylori strains. Real-time PCR was used to detect the point mutations.

Results: A total of 24 out of 63 H. pylori strains (38.1%) were detected as clarithromycin resistant (>0.5 mg l-1 ). The new A2115G (n:6, 25%), A2144T (n:7, 29.1%) and G2141A, 8 (n:8, 33.3%) mutations and the classical A2142G (n:8, 33.3%) and A2143G (n:11, 45.8%) point mutations were detected in the 24 clarithromycin-resistant strains. The A2144T point mutation had the highest median MIC value (3 mg l-1 ) amongst the new mutations, but the classical mutations (A2142G and A2143G) had the highest median MIC values (256 mg l-1 ) overall. The presence of the A2115G (OR:31.66), A2144T (OR:36.92) or G2141A (OR:28.16) mutations increased the likelihood of clarithromycin resistance in H. pylori strains by 31.66-, 36.92- and 28.16-fold (ORs), respectively, according to the binary logistic regression analysis.

Conclusion: We concluded that classical mutations of the 23 S rRNA gene resulted in higher clarithromycin MIC values than new mutations. These new point mutations caused moderate elevations in the MIC values of clarithromycin-resistant H. pylori strains.

Keywords: A2115G, A2144T and G2141A; Helicobacter pylori; clarithromycin; point mutations.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Dyspepsia / epidemiology
  • Dyspepsia / microbiology
  • Female
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Phenotype
  • Point Mutation*
  • Polymorphism, Restriction Fragment Length
  • RNA, Ribosomal, 23S / genetics
  • Real-Time Polymerase Chain Reaction
  • Turkey / epidemiology
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 23S
  • Clarithromycin