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J Clin Med. 2019 Jan 7;8(1). pii: E53. doi: 10.3390/jcm8010053.

Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori.

Author information

1
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. francisnicolai.lauener@uzh.ch.
2
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. imkamp@imm.uzh.ch.
3
INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, 33076 Bordeaux, France. philippe.lehours@u-bordeaux.fr.
4
French National Reference Centre for Campylobacter and Helicobacter, Bordeaux Hospital, 33076 Bordeaux, France. philippe.lehours@u-bordeaux.fr.
5
INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, 33076 Bordeaux, France. alice.buissonniere@chu-bordeaux.fr.
6
French National Reference Centre for Campylobacter and Helicobacter, Bordeaux Hospital, 33076 Bordeaux, France. alice.buissonniere@chu-bordeaux.fr.
7
INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, 33076 Bordeaux, France. lucie.bruhl@chu-bordeaux.fr.
8
French National Reference Centre for Campylobacter and Helicobacter, Bordeaux Hospital, 33076 Bordeaux, France. lucie.bruhl@chu-bordeaux.fr.
9
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. rzbinden@imm.uzh.ch.
10
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. pkeller@imm.uzh.ch.
11
Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland. pkeller@imm.uzh.ch.
12
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. karoline.wagner@usb.ch.

Abstract

Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene.

KEYWORDS:

Helicobacter pylori; antibiotic resistance prediction; laboratory automation; phenotypic drug susceptibility testing; whole genome sequencing

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