ArticleAntimicrobial agents and chemotherapy2014
An in vitro deletion in ribE encoding lumazine synthase contributes to nitrofurantoin resistance in Escherichia coli.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Global prevalence of nitrofurantoin-resistant uropathogenic Escherichia coli (UPEC) in humans: a systematic review and meta-analysis.The Journal of antimicrobial chemotherapy · 2025Pooled it
- Poultry-associated nitrofurantoin-resistant and pre-resistantOne health (Amsterdam, Netherlands) · 2025Article
- Nitrofurantoin resistance mechanisms in uropathogenic Escherichia coli isolates from Iran.Annals of clinical microbiology and antimicrobials · 2025Article
- Mutations in the riboflavin biosynthesis pathway confer resistance to furazolidone and abolish the synergistic interaction between furazolidone and vancomycin inMicrobial genomics · 2025Article
- Unlocking Nitrofurantoin: Understanding Molecular Mechanisms of Action and Resistance in Enterobacterales.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Review
- Genomic characterization of extended-spectrum beta-lactamase-producing and carbapenem-resistant Escherichia coli from urban wastewater in Australia.MicrobiologyOpen · 2024Article
- Article
- Insights into durability against resistance from the antibiotic nitrofurantoin.npj antimicrobials and resistance · 2024Review
- UropathogenicMicroorganisms · 2023Review
- Nitrofurantoin: properties and potential in treatment of urinary tract infection: a narrative review.Frontiers in cellular and infection microbiology · 2023Review
- Assessing the urinary concentration of nitrofurantoin and its antibacterial activity againstFrontiers in veterinary science · 2023Article
- Roseoflavin, a Natural Riboflavin Analogue, PossessesAntimicrobial agents and chemotherapy · 2022Article
- Molecular Insight intoPharmaceuticals (Basel, Switzerland) · 2022Article
- Alterations in chromosomal genesMicrobial genomics · 2021Article
- Fosfomycin and nitrofurantoin: classic antibiotics and perspectives.The Journal of antibiotics · 2021Review
- The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.The Biochemical journal · 2021Article
- Nitrofurans: Revival of an "old" drug class in the fight against antibiotic resistance.PLoS pathogens · 2021Review
- Unraveling Mechanisms and Epidemic Characteristics of Nitrofurantoin Resistance in UropathogenicInfection and drug resistance · 2021Article
- Characterization of Fosfomycin and Nitrofurantoin Resistance Mechanisms inAntibiotics (Basel, Switzerland) · 2020Article
- Novel 5-Nitrofuran-Activating Reductase in Escherichia coli.Antimicrobial agents and chemotherapy · 2019Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTIs), but clinically significant resistance in Escherichia coli is uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal E. coli strains (ST540-p and ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole-genome sequencing was performed for both susceptible isolates and selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a and ST2747-a) and anaerobically (ST540-an and ST2747-an). ST540-a/ST540-an and ST2747-a (aerobic MICs of >64 μg/ml) harbored mutations in the known nitrofurantoin resistance determinants nfsA and/or nfsB, which encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC of 32 μg/ml) and exhibited remarkable growth deficits but did not harbor nfsA/nfsB mutations. We identified a 12-nucleotide deletion in ribE, encoding lumazine synthase, an essential enzyme involved in the biosynthesis of flavin mononucleotide (FMN), which is an important cofactor for NfsA and NfsB. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R E. coli isolates (NRCI-1 to NRCI-6) from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in nfsA and/or nfsB but not ribE. Sequencing of the ribE gene in six intestinal and three urinary E. coli strains showing reduced nitrofurantoin susceptibility (MICs of 16 to 48 μg/ml) also did not identify any relevant mutations. NRCI-1, NRCI-2, and NRCI-5 exhibited up to 4-fold higher anaerobic MICs, compared to the mutants generated in vitro, presumably because of additional mutations in oxygen-sensitive nitroreductases.
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