Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori

Area of Science:

• Medical Microbiology
• Genomics
• Infectious Diseases

Background:

• Helicobacter pylori is a significant human pathogen.
• Current diagnostics for H. pylori infection and antibiotic susceptibility testing (DST) are culture-based, time-consuming, and labor-intensive.
• Whole genome sequencing (WGS) offers a potential rapid alternative for diagnosing bacterial infections and predicting antimicrobial resistance.

Purpose of the Study:

• To evaluate the concordance between phenotypic DST results and WGS-based predictions of antimicrobial resistance in H. pylori.
• To assess the utility of WGS in identifying genetic determinants associated with resistance to key antibiotics.

Main Methods:

• Phenotypic DST for clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was performed on 140 clinical H. pylori isolates using E-Test®.
• Whole genome sequencing (WGS) was employed to identify single nucleotide polymorphisms (SNPs) in specific genes (23S rRNA, gyrA, rpoB, frxA, rdxA, 16S rRNA).

Main Results:

• High congruence (>99%) was observed between phenotypic resistance and WGS-identified SNPs for clarithromycin, levofloxacin, and rifampicin.
• WGS could not reliably predict metronidazole resistance based on identified SNPs in the frxA and rdxA genes.
• All isolates were susceptible to tetracycline, consistent with the absence of specific mutations in the 16S rRNA gene.

Conclusions:

• WGS is a highly accurate tool for predicting H. pylori resistance to clarithromycin, levofloxacin, and rifampicin by detecting specific SNPs.
• Genetic markers for metronidazole resistance in H. pylori require further investigation to improve WGS-based prediction accuracy.
• WGS holds promise for rapid and reliable antimicrobial susceptibility prediction in H. pylori diagnostics.