Related Experiment Video
Updated: Mar 31, 2026
Live-cell Imaging of Fungal Cells to Investigate Modes of Entry and Subcellular Localization of Antifungal Plant Defensins
Published on: December 24, 2017
Human Dectin-1- and Dectin-2-targeted DectiSomes are effective against diverse pathogenic fungi
Suresh Ambati1, Xiaorong Lin2, Zachary A Lewis2
1Department of Genetics, University of Georgia, Athens, Georgia, USA.
Abstract:
Annually, aspergillosis, candidiasis, cryptococcosis, and mucormycosis result in approximately 1,500,000, 650,000, 120,000, and 59,000 deaths, respectively. Mortality rates among patients receiving antifungal drug treatment range from 30% to 90%. Therefore, there is an urgent need to improve the efficacy of antifungal drug therapies against infections by these high-priority fungal diseases. Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, and Rhizopus delemar are the most common causative pathogens. We have previously developed DectiSomes, which are liposomes loaded with antifungal drugs and coated with the carbohydrate recognition domains of mouse Dectin-1 and/or Dectin-2. We demonstrated that the murine DectiSomes efficiently bound and killed these pathogens growing in vitro and/or in mouse disease models. With the plan to move DectiSomes into the clinic with the human Dectin orthologs, we were concerned that the significant sequence divergence between mouse and human Dectin-1 and Dectin-2 carbohydrate recognition domains could have altered pathogen specificity. Herein, we compared the functionality of the human and mouse Dectin-1 and Dectin-2 orthologs in targeting DectiSomes to these pathogens. Binding and growth inhibition data on A. fumigatus and C. neoformans supported their functional similarity, while results with C. albicans and R. delemar indicated some functional divergence. Despite these differences, our results demonstrate that both human and mouse DectiSomes are effective at binding and killing all four diverse fungal pathogens.
Insights
New DectiSomes, liposomes with antifungal drugs, show promise for treating deadly fungal infections. Human and mouse versions effectively target and kill major fungal pathogens, paving the way for clinical use.
Area of Science:
- Mycology
- Immunology
- Drug Delivery
Background:
- High mortality rates from invasive fungal infections (IFIs) underscore the need for improved antifungal therapies.
- Current treatments for aspergillosis, candidiasis, cryptococcosis, and mucormycosis have limited efficacy.
- DectiSomes, liposomes with antifungal drugs and Dectin-1/2 domains, previously showed efficacy against fungal pathogens in vitro and in vivo.
Purpose of the Study:
- To compare the efficacy of human and mouse Dectin-1 and Dectin-2 orthologs in DectiSomes for targeting fungal pathogens.
- To assess potential alterations in pathogen specificity due to sequence divergence between mouse and human Dectin orthologs.
- To evaluate the potential for clinical translation of DectiSomes.
Main Methods:
- DectiSomes were formulated using liposomes loaded with antifungal drugs and coated with human or mouse Dectin-1/2 carbohydrate recognition domains.
- Binding assays were performed to assess DectiSomes' interaction with *Aspergillus fumigatus*, *Candida albicans*, *Cryptococcus neoformans*, and *Rhizopus delemar*.
- Fungal growth inhibition assays were conducted to evaluate the killing efficacy of DectiSomes against these pathogens.
Main Results:
- Both human and mouse DectiSomes demonstrated effective binding and killing of all four fungal pathogens: *A. fumigatus*, *C. albicans*, *C. neoformans*, and *R. delemar*.
- Functional similarity was observed between human and mouse Dectin orthologs when targeting *A. fumigatus* and *C. neoformans*.
- Some functional divergence was noted with *C. albicans* and *R. delemar*, indicating differential targeting efficiencies.
Conclusions:
- Despite minor functional divergence, both human and mouse DectiSomes are effective against a broad spectrum of fungal pathogens.
- The findings support the potential of DectiSomes as a viable therapeutic strategy for invasive fungal infections.
- Further development of DectiSomes, utilizing human Dectin orthologs, is warranted for clinical applications.
Related Concept Videos
01:15Antifungal Agents
01:23Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
01:28Fungal Phylum Microsporidia
01:15Anthelminthic Agents
01:28Diphtheria