Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny

Tal Domanovich-Asor, Hillary A. Craddock, Yair Motro, Boris Khalfin, Avi Peretz, Jacob Moran-Gilad

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny. Materials/methods: A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in-house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST). Results: Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences). Conclusions: This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.

Original languageEnglish
Article numbere12782
JournalHelicobacter
Volume26
Issue number2
DOIs
StatePublished - Apr 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 John Wiley & Sons Ltd.

Keywords

  • Antimicrobial resistance
  • cgMLST
  • global epidemiology
  • Helicobacter pylori
  • Whole Genome Sequencing

ASJC Scopus subject areas

  • Gastroenterology
  • Infectious Diseases

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