Helicobacter pylori frxA mutation conferring resistance to metronidazole

Accession ARO:3007059
CARD Short NameHpyl_fxrA_MTZ
DefinitionFrxA encodes an NADH-flavin oxidoreductase in Helicobacter pylori. Mutations in this gene confer resistance to nitrofuran antibiotics and metronidazole.
AMR Gene FamilyAntibiotic resistant Helicobacter pylori nitroreductase
Drug Classnitroimidazole antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsHelicobacter pylorig
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ Antibiotic resistant Helicobacter pylori nitroreductase [AMR Gene Family]
+ confers_resistance_to_antibiotic metronidazole [Antibiotic]

Justino MC, et al. 2014. FEBS J 281(19):4495-505 FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity. (PMID 25132107)

Miftahussurur M, et al. 2016. BMC Microbiol 16(1):256 Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal. (PMID 27809767)

Tanih NF, et al. 2011. Ann Trop Med Parasitol 105(3):251-9 Characterisation of the genes encoding resistance to metronidazole (rdxA and frxA) and clarithromycin (the 23S-rRNA genes) in South African isolates of Helicobacter pylori. (PMID 21801504)

Lauener FN, et al. 2019. J Clin Med 8(1): Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori. (PMID 30621024)

Zhang Y, et al. 2020. Infect Drug Resist 13:311-322 Mutations in the Antibiotic Target Genes Related to Clarithromycin, Metronidazole and Levofloxacin Resistance in Helicobacter pylori Strains from Children in China. (PMID 32099422)

Somi MH, et al. 2017. Trop Biomed 34(2):346-351 Evaluation of frxA and rdxA gene mutations in clinical metronidazole resistance Helicobacter pylori isolates. (PMID 33593015)


Prevalence of Helicobacter pylori frxA mutation conferring resistance to metronidazole among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 381 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Helicobacter pylori32.31%0%0%0%
Show Perfect Only

Detection Models

Model Type: protein variant model

Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.

Bit-score Cut-off (blastP): 420


  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 27809767R106fs A15V,I144V,M66I R3T A15V P41L 45615,M21V,A80T,Q119STOP+45620,A70V 45615,N73STOP+45620,R3T 45615,Q11STOP+45620,Q5STOP R86STOP
PMID: 21801504E199STOP L39STOP 45615,E27V+45620,V44G,Y60F 45615,L717F,Q113STOP+45620,L39STOP
PMID: 30621024K105STOP M149STOP A16T A192STOP V7I A32V S43A I44F Y62D A85V I117M M126F
PMID: 32099422C13A A48G G441A
PMID: 33593015V9I A70G K97E

>gb|AAD07703.1|+|Helicobacter pylori frxA mutation conferring resistance to metronidazole [Helicobacter pylori 26695]

>gb|AE000511.1|+|687928-688581|Helicobacter pylori frxA mutation conferring resistance to metronidazole [Helicobacter pylori 26695]