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A Falciformispora senegalensis grain model in Galleria mellonella larvae
Jingyi Ma1, Mickey Konings1, Annelies Verbon1
1Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract:
Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black or white, and the consistency and morphology differs per causative agent. The two most common causative agents of black-grain eumycetoma are Madurella mycetomatis and Falciformispora senegalensis. Since grains cannot be formed in vitro, in vivo models are needed to study grain formation. Here, we used the invertebrate Galleria mellonella to establish an in vivo grain model for F. senegalensis. Three different F. senegalensis strains were selected, and four different inocula were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 10 mg/larvae. Larval survival was monitored for 10 days. Grain formation was studied macroscopically and histologically. The efficacy of antifungal therapy was determined for itraconazole, amphotericin B, and terbinafine. A concentration of 10 mg F. senegalensis per larva was lethal for the majority of the larvae within 10 days. At this inoculum, grains were formed within 24 h after infection. The grains produced in the larvae resembled those formed in human patients. Amphotericin B given at 1 mg/kg 4 h, 28 h, and 52 h after infection prolonged larval survival. No enhanced survival was noted for itraconazole or terbinafine. In conclusion, we developed a F. senegalensis grain model in G. mellonella larvae in which grains were formed that were similar to those formed in patients. This model can be used to monitor grain formation over time and study antifungal efficacy.
Insights
Researchers developed a new in vivo model using Galleria mellonella (G. mellonella) larvae to study eumycetoma grain formation by Falciformispora senegalensis (F. senegalensis). This model successfully replicated patient-like grains and can aid in antifungal drug development.
Area of Science:
- Mycology
- Infectious Diseases
- Invertebrate Models
Background:
- Eumycetoma is a fungal infection characterized by grain formation, crucial for diagnosis.
- Falciformispora senegalensis (F. senegalensis) is a common cause of black-grain eumycetoma.
- In vitro studies cannot replicate eumycetoma grain formation, necessitating in vivo models.
Purpose of the Study:
- To establish an in vivo model for studying F. senegalensis grain formation using Galleria mellonella (G. mellonella) larvae.
- To assess the efficacy of antifungal agents against F. senegalensis in this new model.
Main Methods:
- Infection of G. mellonella larvae with three F. senegalensis strains at varying inocula (0.04–10 mg/larva).
- Monitoring of larval survival for 10 days post-infection.
- Macroscopic and histological examination of grain formation and assessment of antifungal treatment (itraconazole, amphotericin B, terbinafine).
Main Results:
- A 10 mg/larva inoculum of F. senegalensis was lethal and induced grain formation within 24 hours.
- Grains formed in G. mellonella larvae were histologically similar to those found in human eumycetoma.
- Amphotericin B treatment prolonged larval survival, unlike itraconazole or terbinafine.
Conclusions:
- A novel and effective in vivo model for F. senegalensis eumycetoma grain formation was developed using G. mellonella larvae.
- This model mimics human disease pathology and can be utilized for studying grain development and evaluating antifungal therapies.
- The model shows promise for future research into eumycetoma treatment strategies.
