ArticleAntimicrobial agents and chemotherapy2015
Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Article
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- Functional determination of site-mutations inFrontiers in cell and developmental biology · 2024Article
- OptimizingGut and liver · 2023Review
- Whole Genome Sequencing for StudyingAntibiotics (Basel, Switzerland) · 2023Article
- Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance.Clinical microbiology reviews · 2022Review
- A Survey ofAntimicrobial agents and chemotherapy · 2022Article
- Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance fromBiomolecules · 2022Review
- Automated extraction of genes associated with antibiotic resistance from the biomedical literature.Database : the journal of biological databases and curation · 2022Article
- Prevalence of antibiotic resistance ofAmerican journal of translational research · 2022Article
- Correlation Analysis Among Genotype Resistance, Phenotype Resistance, and Eradication Effect After Resistance-Guided Quadruple Therapies in RefractoryFrontiers in microbiology · 2022Article
- Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications.Nature reviews. Gastroenterology & hepatology · 2021Review
- Molecular testing for H. pylori clarithromycin and quinolone resistance: a prospective Chinese study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Next Generation Sequencing for the Prediction of the Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2021Review
- Prediction of Streptococcus uberis clinical mastitis treatment success in dairy herds by means of mass spectrometry and machine-learning.Scientific reports · 2021Article
- Whole-Genome Sequencing and Comparative Genomics of ThreePathogens (Basel, Switzerland) · 2021Article
- A comparative whole genome analysis of Helicobacter pylori from a human dense South Asian setting.Helicobacter · 2021Article
- Phenotypic and Genotypic Analysis of ResistantDiagnostics (Basel, Switzerland) · 2020Article
- Genotype profiles ofTherapeutic advances in gastroenterology · 2020Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance.
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