ArticleThe Journal of antimicrobial chemotherapy2014
Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- A drug-microbiome-drug interaction impacts co-prescribed medications for Parkinson's disease.Nature microbiology · 2026Article
- The Ambivalent Nature ofToxins · 2025Review
- Phase-Specific Antibiotic Resistance Mechanisms in anbioRxiv : the preprint server for biology · 2025Article
- Differential impacts of hemin and free iron on amoxicillin susceptibility inFrontiers in microbiology · 2025Article
- New functions of pirin proteins and a 2-ketoglutarate: Ferredoxin oxidoreductase ortholog in Bacteroides fragilis metabolism and their impact on antimicrobial susceptibility to metronidazole and amixicile.MicrobiologyOpen · 2024Article
- Proteomics-Based RT-qPCR and Functional Analysis of 18 Genes in Metronidazole Resistance ofAntibiotics (Basel, Switzerland) · 2024Article
- Recent Trends in Antimicrobial Resistance among Anaerobic Clinical Isolates.Microorganisms · 2023Review
- Proteomic analysis of metronidazole resistance in the human facultative pathogenFrontiers in microbiology · 2023Article
- A general protocol for the expression and purification of the intact transmembrane transporter FeoB.Biochimica et biophysica acta. Biomembranes · 2022Article
- Modulation of Iron Import and Metronidazole Resistance inFrontiers in microbiology · 2022Article
- Article
- Chromosomal Resistance to Metronidazole in Clostridioides difficile Can Be Mediated by Epistasis between Iron Homeostasis and Oxidoreductases.Antimicrobial agents and chemotherapy · 2020Article
- TheInfection and immunity · 2020Article
- Whole-Genome Analysis of Two Copies ofInfection and drug resistance · 2020Article
- Bacteroides fragilis requires the ferrous-iron transporter FeoAB and the CobN-like proteins BtuS1 and BtuS2 for assimilation of iron released from heme.MicrobiologyOpen · 2019Article
- Generation of Markerless Deletions in the Nosocomial PathogenApplied and environmental microbiology · 2019Article
- Three metronidazole-resistant Prevotella bivia strains harbour a mobile element, encoding a novel nim gene, nimK, and an efflux small MDR transporter.The Journal of antimicrobial chemotherapy · 2018Article
- Toward a mechanistic understanding of Feo-mediated ferrous iron uptake.Metallomics : integrated biometal science · 2018Review
- Anaerobic utilization of Fe(III)-xenosiderophores among Bacteroides species and the distinct assimilation of Fe(III)-ferrichrome by Bacteroides fragilis within the genus.MicrobiologyOpen · 2017Article
- nim gene-independent metronidazole-resistant Bacteroides fragilis in surgical site infections.GMS hygiene and infection control · 2017Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMetronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear.
methodsA transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole.
resultsThirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo.
conclusionsSelection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis.
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