ArticleAntimicrobial agents and chemotherapy2012
Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 114 citations in OpenAlex.
- Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.BioMed research international · 2017Trial
- Trial
- Antifungal activities and toxicity studies of water-soluble non-steroidal analgesic salts.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Isw2-mediated chromatin remodeling governs antifungal tolerance and heteroresistance in Candida albicans.npj antimicrobials and resistance · 2026Article
- Article
- Leveraging Vulnerabilities in Copper Trafficking for Synergistic Antifungal Activity.ACS chemical biology · 2025Article
- Caspofungin binding to iron compromises its antifungal efficacy against Candida albicans.Communications biology · 2025Article
- Transcriptional control ofmBio · 2025Article
- The role of gene copy number variation in antimicrobial resistance in human fungal pathogens.npj antimicrobials and resistance · 2025Review
- Functional genomic analysis of genes important for Candida albicans fitness in diverse environmental conditions.Cell reports · 2024Article
- In vitro combination with doxycycline plus antifungals against clinical Mucorales pathogens.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond.Antibiotics (Basel, Switzerland) · 2022Review
- Competition for Iron during Polymicrobial Infections May Increase Antifungal Drug Susceptibility-How Will It Impact Treatment Options?Infection and immunity · 2022Article
- Pseudomonas Synergizes with Fluconazole againstInfection and immunity · 2022Article
- Copper Acts Synergistically With Fluconazole inFrontiers in microbiology · 2022Article
- SAGA Complex Subunits inFrontiers in cellular and infection microbiology · 2022Article
- Effect of iron chelation on anti-pseudomonal activity of doxycycline.International journal of antimicrobial agents · 2021Article
- Evaluation of the Synergistic Activity of Antibacterial and Antifungal Drugs against Candida auris Using an Inkjet Printer-Assisted Method.Antimicrobial agents and chemotherapy · 2021Article
- Drug repurposing strategies in the development of potential antifungal agents.Applied microbiology and biotechnology · 2021Review
- Antifungal Activity of Minocycline and Azoles Against Fluconazole-ResistantFrontiers in microbiology · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of ERG11 in Saccharomyces cerevisiae but not in C. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.