Helicobacter pylori rdxA mutation conferring resistance to metronidazole

Download Sequences
Accession ARO:3007055
CARD Short NameHpyl_rdxA_MTZ
DefinitionThe rdxA gene in Helicobacter pylori encodes an NADPH nitroreductase. Mutations in this gene are associated with metronidazole resistance.
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

Rasheed F, et al. 2014. Helicobacter 19(5):387-99 Analysis of clinical isolates of Helicobacter pylori in Pakistan reveals high degrees of pathogenicity and high frequencies of antibiotic resistance. (PMID 24827414)

Goodwin A, et al. 1998. Mol Microbiol 28(2):383-93 Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. (PMID 9622362)

Tankovic J, et al. 2000. Antimicrob Agents Chemother 44(3):608-13 Frequent association between alteration of the rdxA gene and metronidazole resistance in French and North African isolates of Helicobacter pylori. (PMID 10681326)

Farzi N, et al. 2019. J Clin Med 8(11): High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. (PMID 31744181)

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)

Guzman K, et al. 2023. Front Microbiol 14:1198325 The Helicobacter pylori single nucleotide polymorphisms SNPs associated with multiple therapy resistance in Colombia. (PMID 37485536)
Resistomes

Prevalence of Helicobacter pylori rdxA 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 pylori73.59%0%67.33%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): 400

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
A1Gsingle resistance variantPMID:31744181
Q5Ternonsense mutationPMID:31744181
L13fsframeshift mutationPMID:27809767
R16H,S108A,R176C,S196Nmultiple resistance variantsPMID:27809767
R16Hsingle resistance variantPMID:24827414
R16Csingle resistance variantPMID:24827414
C18fsframeshift mutationPMID:30621024
C19Ysingle resistance variantPMID:24827414
T31Esingle resistance variantPMID:24827414
T38fsframeshift mutationPMID:30621024
G47Asingle resistance variantPMID:32099422
C49Tsingle resistance variantPMID:32099422
A50Ternonsense mutationPMID:30621024
Q50Ternonsense mutationPMID:31744181
D59Ssingle resistance variantPMID:37485536
D59Ternonsense mutationPMID:37485536
D59Nsingle resistance variantPMID:33593015
G60Asingle resistance variantPMID:32099422
T62fsframeshift mutationPMID:30621024
K64Nsingle resistance variantPMID:9622362
A67Vsingle resistance variantPMID:10681326
A68Esingle resistance variantPMID:9622362
N73Ternonsense mutationPMID:27809767
R90Ksingle resistance variantPMID:24827414
A96fsframeshift mutationPMID:30621024
H97Ysingle resistance variantPMID:33593015
H97Tsingle resistance variantPMID:24827414
P106Ssingle resistance variantPMID:9622362
S108Asingle resistance variantPMID:24827414
G112fsframeshift mutationPMID:30621024
A118Ssingle resistance variantPMID:24827414
A118Tsingle resistance variantPMID:24827414
C148Ysingle resistance variantPMID:27809767
T162fsframeshift mutationPMID:30621024
T184Gsingle resistance variantPMID:32099422
G189Ssingle resistance variantPMID:27809767
G189Csingle resistance variantPMID:24827414
A190fsframeshift mutationPMID:30621024
L210Vsingle resistance variantPMID:33593015
C273Tsingle resistance variantPMID:32099422
45615,E27V+45620,V44G,Y60Fco-dependent single resistance variantPMID:21801504
45615,M21V,A80T,Q119Ter+45620,A70Vco-dependent single resistance variantPMID:27809767
45615,N73Ter+45620,R3Tco-dependent single resistance variantPMID:27809767
45615,Q11Ter+45620,Q5Terco-dependent nonsense SNPPMID:27809767

>gb|WP_000670110.1|-|Helicobacter pylori rdxA mutation conferring resistance to metronidazole [Helicobacter pylori]
MKFLDQEKRRQLLNERHSCKMFDSHYEFSSTELEEIAEIARLSPSSYNTQPWHFVMVTDK
DLKKQIAAHSYFNEEMIKSASALMVVCSLRPSELLPHGHYMQNLYPESYKVRVIPSFAQM
LGVRFNHSMQRLESYILEQCYIAVGQICMGVSLMGLDSCIIGGFDPLKVGEVLEERINKP
KIACLIALGKRVAEASQKSRKSKVDAITWL


>gb|NC_000915.1|-|1013553-1014185|Helicobacter pylori rdxA mutation conferring resistance to metronidazole [Helicobacter pylori]
ATGAAATTTTTGGATCAAGAAAAAAGAAGACAATTATTAAACGAGCGCCATTCTTGCAAGATGTTTGATAGCCATTATGAGTTTTCTAGC
ACAGAATTAGAAGAAATCGCTGAAATCGCCAGGCTATCGCCAAGCTCTTACAACACGCAGCCATGGCATTTTGTGATGGTTACTGATAAG
GATTTAAAAAAACAAATTGCAGCGCACAGCTATTTCAATGAAGAGATGATTAAAAGCGCTTCAGCGTTAATGGTGGTATGCTCTTTAAGA
CCCAGCGAGTTGTTACCACACGGCCACTACATGCAAAATCTCTATCCGGAGTCTTATAAAGTTAGAGTGATCCCCTCTTTTGCTCAAATG
CTTGGCGTGAGATTCAACCACAGCATGCAAAGATTAGAAAGCTATATTTTAGAGCAATGCTATATCGCTGTGGGGCAAATTTGCATGGGC
GTGAGCTTAATGGGATTGGATAGTTGCATTATTGGAGGCTTTGATCCTTTAAAGGTGGGCGAAGTTTTAGAAGAGCGTATCAATAAGCCT
AAAATCGCATGCTTGATCGCTTTGGGCAAGAGGGTGGCAGAAGCGAGTCAAAAATCAAGAAAATCAAAAGTTGATGCGATTACTTGGTTG
TGA

Curator Acknowledgements
Curator Description Most Recent Edit