Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori

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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli H. pylori isolates (n = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our in-house bioinformatics pipeline targeting point mutations in the relevant genes (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in H. pylori cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of H. pylori isolates demonstrates that inferring resistance phenotypes from WGS in H. pylori remains challenging and should be optimized further.

Original languageEnglish GB
Article number2
Pages (from-to)1-9
Number of pages9
JournalMicroorganisms
Volume9
Issue number1
DOIs
StatePublished - 1 Jan 2021

Keywords

  • Clinical antimicrobial susceptibility testing
  • H. pylori
  • Whole genome sequencing (WGS)

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Virology

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