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An invertebrate infection model for evaluating anti-fungal agents against dermatophytosis
Masaki Ishii1, Yasuhiko Matsumoto2, Tsuyoshi Yamada2
1Genome Pharmaceuticals Institute Co. Ltd., 102 Next Building, 3-24-17 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Abstract:
Animal models of pathogenic infection are needed to evaluate candidate compounds for the development of anti-infectious drugs. Dermatophytes are pathogenic fungi that cause several infectious diseases. We established a silkworm dermatophyte infection model to evaluate anti-fungal drugs. Injection of conidia of the dermatophyte Arthroderma vanbreuseghemii into silkworms was lethal. A. vanbreuseghemii conidia germinated in liquid culture were more potent against silkworms than non-germinated conidia. Germinated conidia of other dermatophytes, Arthroderma benhamiae, Trichophyton rubrum, and Microsporum canis, also killed silkworms. Injection of heat-treated germinated A. vanbreuseghemii conidia did not kill silkworms, suggesting that only viable fungi are virulent. Injecting terbinafine or itraconazole, oral drugs used clinically to treat dermatophytosis, into the silkworm midgut had therapeutic effects against infection with germinated A. vanbreuseghemii conidia. When silkworms were injected with A. vanbreuseghemii expressing enhanced green fluorescent protein (eGFP), mycelial growth of the fungus was observed in the fat body and midgut. Injection of terbinafine into the silkworm midgut, which corresponds to oral administration in humans, inhibited the growth of A. vanbreuseghemii expressing eGFP in the fat body. These findings suggest that the silkworm infection model with eGFP-expressing dermatophytes is useful for evaluating the therapeutic activity of orally administered anti-fungal agents against dermatophytes.
Insights
A novel silkworm infection model effectively evaluates antifungal drugs against dermatophytes. This model uses germinated fungal conidia and shows therapeutic effects of terbinafine and itraconazole, aiding new anti-infective drug development.
Area of Science:
- Mycology
- Infectious Diseases
- Drug Discovery
Background:
- Dermatophytes cause significant human fungal infections.
- Effective animal models are crucial for developing new antifungal therapies.
- Current models may not fully represent human oral drug administration.
Purpose of the Study:
- To establish and validate a silkworm infection model for evaluating antifungal drugs against dermatophytes.
- To assess the efficacy of terbinafine and itraconazole in this model.
- To determine the model's suitability for testing orally administered antifungals.
Main Methods:
- Infection of silkworms with dermatophyte conidia (Arthroderma vanbreuseghemii, A. benhamiae, T. rubrum, M. canis).
- Evaluation of fungal viability and virulence using heat-treated conidia.
- Administration of terbinafine and itraconazole into the silkworm midgut.
- Utilizing eGFP-expressing A. vanbreuseghemii to visualize fungal growth.
Main Results:
- Germinated dermatophyte conidia were lethal to silkworms, with viable fungi being virulent.
- Terbinafine and itraconazole demonstrated therapeutic effects against dermatophyte infection in silkworms.
- The silkworm model successfully visualized fungal growth in the fat body and midgut.
- Oral terbinafine administration inhibited fungal growth, mimicking human treatment.
Conclusions:
- The silkworm serves as a viable and effective infection model for dermatophytes.
- This model accurately reflects the therapeutic activity of orally administered antifungal agents.
- The eGFP-expressing dermatophyte system enhances visualization and evaluation within the model.
