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Updated: May 13, 2026
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
A zinc-chelating cyclic alkyl polyamine compound is efficient and safe in a murine model of multidrug-resistant
Takayuki Shinohara1, Akira Wada2, Masahiro Abe1
1Department of Fungal Infection, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Abstract:
Candida auris is an emerging multidrug-resistant fungal pathogen associated with severe nosocomial outbreaks and high mortality rates worldwide. The increasing incidence of antifungal resistance underscores the urgent need for agents with novel mechanisms of action. APC6 is a zinc-chelating cyclic alkyl polyamine compound that selectively disrupts zinc homeostasis in fungal cells. We have previously reported that APC6 has antifungal activity against Candida spp., including Candida auris, and low cytotoxicity to human cells. In this study, we evaluated the in vivo efficacy and safety of APC6 using a neutropenic murine model of disseminated C. auris infection. APC6 significantly improved survival and reduced fungal burden in the liver, kidneys, and brain. At a therapeutic dose of 15 mg/kg, APC6 had similar or superior antifungal activity to that of amphotericin B. Histopathological analysis revealed a decreased number of fungal microabscesses in APC6-treated tissues. No significant adverse effects were observed following 28-day repeated intraperitoneal administration, and the Ames assay revealed no mutagenic activity. To our knowledge, this is the first study to demonstrate that a zinc-chelating compound can improve survival and reduce organ fungal burden in a mammalian model of drug-resistant C. auris infection. These results highlight APC6 as a promising lead compound targeting fungal zinc homeostasis and support its further development as a novel antifungal agent.
Insights
A novel zinc-chelating compound, APC6, demonstrated significant efficacy against multidrug-resistant Candida auris in a mouse model. APC6 improved survival and reduced fungal burden, showing promise as a new antifungal agent.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Candida auris is a multidrug-resistant fungus causing severe infections worldwide.
- Antifungal resistance necessitates novel therapeutic agents with new mechanisms of action.
Purpose of the Study:
- To evaluate the in vivo efficacy and safety of APC6, a zinc-chelating compound, against Candida auris.
- To assess APC6's potential as a novel antifungal agent targeting fungal zinc homeostasis.
Main Methods:
- A neutropenic murine model of disseminated Candida auris infection was utilized.
- APC6 efficacy was assessed by survival rates and fungal burden in organs (liver, kidneys, brain).
- Safety was evaluated through repeated administration and mutagenicity testing (Ames assay).
Main Results:
- APC6 significantly improved survival and reduced fungal burden in multiple organs.
- APC6 demonstrated antifungal activity comparable or superior to amphotericin B.
- No significant adverse effects or mutagenic activity were observed with APC6 treatment.
Conclusions:
- APC6 is the first demonstrated zinc-chelating compound to improve survival in a mammalian model of drug-resistant Candida auris infection.
- APC6 shows significant potential as a novel antifungal agent by targeting fungal zinc homeostasis.
- Further development of APC6 is supported by its efficacy and safety profile.
