Helicobacter pylori rdxA mutation conferring resistance to metronidazole

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 413 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 pylori73.59%0%52.48%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

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 24827414R16C R16H C19Y T31E R90K H97T S108A A118T A118S G189C
PMID: 9622362K64N A68E P106S
PMID: 10681326A67V
PMID: 31744181A1G Q50STOP Q5STOP
PMID: 27809767L13fs C148Y R16H,S108A,R176C,S196N G189S 45615,M21V,A80T,Q119STOP+45620,A70V 45615,N73STOP+45620,R3T 45615,Q11STOP+45620,Q5STOP N73STOP
PMID: 2180150445615,E27V+45620,V44G,Y60F
PMID: 30621024G112fs T162fs C18fs A190fs T38fs A50STOP T62fs A96fs
PMID: 32099422G47A C49T G60A T184G C273T
PMID: 33593015D59N H97Y L210V
PMID: 37485536D59S D59STOP

>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