ArticleEukaryotic cell2012
Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.
Article in Eukaryotic cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
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- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in pathogenic Mucor fungi.PLoS biology · 2026Article
- Epimutations driven by RNAi or heterochromatin evoke transient antimicrobial drug resistance in fungi.bioRxiv : the preprint server for biology · 2025Article
- RNAi epimutations conferring antifungal drug resistance are inheritable.Nature communications · 2025Article
- Rapamycin Plays a Pivotal Role in the Potent Antifungal Activity Exhibited AgainstMicroorganisms · 2025Article
- Non-dikarya fungi share the TORC1 pathway with animals, not with Saccharomyces cerevisiae.Scientific reports · 2025Article
- The TOR signalling pathway in fungal phytopathogens: A target for plant disease control.Molecular plant pathology · 2024Review
- Article
- Experimental Models to Study the Pathogenesis and Treatment of Mucormycosis.Journal of fungi (Basel, Switzerland) · 2024Review
- Autophagy Modulation and Its Implications on Glioblastoma Treatment.Current issues in molecular biology · 2023Review
- Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections.Journal of fungi (Basel, Switzerland) · 2023Review
- Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents.European journal of medicinal chemistry · 2023Review
- Natural product ligands of FKBP12: Immunosuppressive antifungal agents FK506, rapamycin, and beyond.PLoS pathogens · 2023Article
- Current Treatment Options for COVID-19 Associated Mucormycosis: Present Status and Future Perspectives.Journal of clinical medicine · 2022Review
- Target of rapamycin controls hyphal growth and pathogenicity through FoTIP4 in Fusarium oxysporum.Molecular plant pathology · 2021Article
- Current cancer therapies and their influence on glucose control.World journal of diabetes · 2021Review
- Drug repurposing strategies in the development of potential antifungal agents.Applied microbiology and biotechnology · 2021Review
- Donor-derived renal allograft mucormycosis in a combined liver and kidney transplantation: Case report and review of the literature.Transplant infectious disease : an official journal of the Transplantation Society · 2021Review
- The TOR kinase pathway is relevant for nitrogen signaling and antagonism of the mycoparasite Trichoderma atroviride.PloS one · 2021Article
- Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi.Memorias do Instituto Oswaldo Cruz · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M. circinelloides are mediated via conserved complexes with FKBP12 and a Tor homolog. We found that spontaneous mutations that disrupted conserved residues in FKBP12 conferred rapamycin and FK506 resistance. Disruption of the FKBP12-encoding gene, fkbA, also conferred rapamycin and FK506 resistance. Expression of M. circinelloides FKBP12 (McFKBP12) complemented a Saccharomyces cerevisiae mutant strain lacking FKBP12 to restore rapamycin sensitivity. Expression of the McTor FKBP12-rapamycin binding (FRB) domain conferred rapamycin resistance in S. cerevisiae, and McFKBP12 interacted in a rapamycin-dependent fashion with the McTor FRB domain in a yeast two-hybrid assay, validating McFKBP12 and McTor as conserved targets of rapamycin. We showed that in vitro, rapamycin exhibited potent growth inhibitory activity against M. circinelloides. In a Galleria mellonella model of systemic mucormycosis, rapamycin improved survival by 50%, suggesting that rapamycin and nonimmunosuppressive analogs have the potential to be developed as novel antifungal therapies for treatment of patients with mucormycosis.
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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.