Helicobacter pylori frxA mutation conferring resistance to metronidazole

Download Sequences
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+wgs
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic metronidazole [Antibiotic]
+ Antibiotic resistant Helicobacter pylori nitroreductase [AMR Gene Family]
Publications

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)
Resistomes

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 414 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 GIGRDI-AMR2
Helicobacter pylori32.31%0%34.61%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

PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).

MutationMutation typePubMed
R3Tsingle resistance variantPMID:27809767
V7Isingle resistance variantPMID:30621024
V9Isingle resistance variantPMID:33593015
C13Asingle resistance variantPMID:32099422
A15Vsingle resistance variantPMID:27809767
A15V,I144V,M66Imultiple resistance variantsPMID:27809767
A16Tsingle resistance variantPMID:30621024
A32Vsingle resistance variantPMID:30621024
L39Ternonsense mutationPMID:21801504
P41Lsingle resistance variantPMID:27809767
S43Asingle resistance variantPMID:30621024
I44Fsingle resistance variantPMID:30621024
A48Gsingle resistance variantPMID:32099422
Y62Dsingle resistance variantPMID:30621024
A70Gsingle resistance variantPMID:33593015
A85Vsingle resistance variantPMID:30621024
R86Ternonsense mutationPMID:27809767
K97Esingle resistance variantPMID:33593015
K105Ternonsense mutationPMID:30621024
R106fsframeshift mutationPMID:27809767
I117Msingle resistance variantPMID:30621024
M126Fsingle resistance variantPMID:30621024
M149Ternonsense mutationPMID:30621024
A192Ternonsense mutationPMID:30621024
E199Ternonsense mutationPMID:21801504
G441Asingle resistance variantPMID:32099422
45615,L717F,Q113Ter+45620,L39Terco-dependent single resistance variantPMID:21801504
45615,Q11Ter+45620,Q5Terco-dependent nonsense SNPPMID:27809767
45615,M21V,A80T,Q119Ter+45620,A70Vco-dependent single resistance variantPMID:27809767
45615,N73Ter+45620,R3Tco-dependent single resistance variantPMID:27809767
45615,E27V+45620,V44G,Y60Fco-dependent single resistance variantPMID:21801504

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


>gb|AE000511.1|+|687928-688581|Helicobacter pylori frxA mutation conferring resistance to metronidazole [Helicobacter pylori 26695]
ATGGACAGAGAACAAGTGGTTGCTTTACAGCACCAACGATTTGCTGCAAAAAAATACGATCCTAATCGTCGTATTTCCCAAAAGGATTGG
GAAGCTTTGGTTGAAGTGGGGAGATTAGCCCCTTCTTCAATCGGGCTTGAACCATGGAAAATGCTTTTATTGAAAAATGAACGCATGAAA
GAAGATTTAAAACCGATGGCCTGGGGGGCGCTTTTTGGTTTGGAGGGAGCGAGCCATTTTGTCATTTATCTTGCGCGAAAAGGCGTTACT
TATGACAGCGATTACGTTAAAAAAGTGATGCATGAGGTTAAAAAAAGGGATTATGACACTAATTCTAGGTTCGCTCAAATCATCAAAAAT
TTCCAAGAGAACGATATGAAACTCAATAGCGAACGATCTTTGTTTGATTGGGCTAGCAAGCAGACTTATATCCAAATGGCGAACATGATG
ATGGCAGCGGCCATGTTAGGGATTGATTCTTGCCCGATTGAAGGGTATGATCAAGAAAAAGTGGAGGCTTATTTAGAGGAAAAAGGCTAT
CTGAACACGGCGGAATTTGGCGTGTCGGTAATGGCTTGTTTTGGTTATCGTAACCAAGAAATCACCCCTAAAACCCGCTGGAAGACAGAA
GTTATTTATGAAGTGATTGAATAA

Curator Acknowledgements
Curator Description Most Recent Edit