ArticlePloS one2013
Mitochondrial respiratory pathways inhibition in Rhizopus oryzae potentiates activity of posaconazole and itraconazole via apoptosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.Journal of fungi (Basel, Switzerland) · 2025Article
- Marine-Derived Metabolites Act as Promising Antifungal Agents.Marine drugs · 2024Review
- Article
- Antifungal Activity and Potential Mechanism of Panobinostat in Combination With Fluconazole AgainstFrontiers in microbiology · 2020Article
- High Efficiency Drug Repurposing Design for New Antifungal Agents.Methods and protocols · 2019Article
- The Synergistic Antifungal Effect and Potential Mechanism of D-Penicillamine Combined With Fluconazole AgainstFrontiers in microbiology · 2019Article
- Effect of the Novel Antifungal Drug F901318 (Olorofim) on Growth and Viability of Aspergillus fumigatus.Antimicrobial agents and chemotherapy · 2018Article
- Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal Tolerance.Molecules (Basel, Switzerland) · 2017Article
- Regulated Forms of Cell Death in Fungi.Frontiers in microbiology · 2017Review
- Article
- Micafungin induced apoptosis inMicrobial cell (Graz, Austria) · 2015Article
- Purification and characterization of a cytochrome c with novel caspase-3 activation activity from the pathogenic fungus Rhizopus arrhizus.BMC biochemistry · 2015Article
- Article
- Iron starvation induces apoptosis in Rhizopus oryzae in vitro.Virulence · 2015Article
- Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles againstMicrobial cell (Graz, Austria) · 2014Article
- Use of benzo analogs to enhance antimycotic activity of kresoxim methyl for control of aflatoxigenic fungal pathogens.Frontiers in microbiology · 2014Article
- Proven invasive pulmonary mucormycosis successfully treated with amphotericin B and surgery in patient with acute myeloblastic leukemia: a case report.Journal of medical case reports · 2013Article
- Update on mucormycosis pathogenesis.Current opinion in infectious diseases · 2013Review
- Hyperthermia sensitizes Rhizopus oryzae to posaconazole and itraconazole action through apoptosis.Antimicrobial agents and chemotherapy · 2013Article
- The calcineurin pathway inhibitor tacrolimus enhances the in vitro activity of azoles against Mucorales via apoptosis.Eukaryotic cell · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The incidence of mucormycosis has increased drastically in immunocompromised patients. Also the array of targets whose inhibition results in Mucorales death is limited. Recently, researchers identified mitochondria as important regulators of detoxification and virulence mechanisms in fungi. In this context, targeting the mitochondrial respiratory chain may provide a new platform for antifungal development. We hypothesized that targeting respiratory pathways potentiates triazoles activity via apoptosis. We found that simultaneous administration of antimycin A (AA) and benzohydroxamate (BHAM), inhibitors of classical and alternative mitochondrial pathways respectively, resulted in potent activity of posaconazole (PCZ) and itraconazole (ICZ) against Rhizopus oryzae. We observed cellular changes characteristic of apoptosis in R. oryzae cells treated with PCZ or ICZ in combination with AA and BHAM. The fungicidal activity of this combination against R. oryzae was correlated with intracellular reactive oxygen species accumulation (ROS), phosphatidylserine externalization, mitochondrial membrane depolarization, and increased caspase like activity. DNA fragmentation and condensation assays also revealed apoptosis of R. oryzae cells. These apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine. Taken together, these findings suggest that the use of PCZ or ICZ in combination with AA and BHAM makes R. oryzae exquisitely sensitive to treatment with triazoles via apoptosis. This strategy may serve as a new model for the development of improved or novel antifungal agents.
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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.