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Published on: November 28, 2019
Direct Visualization of Fungal Burden in Filamentous Fungus-Infected Silkworms
Yidong Yu1,2, Ann-Katrin Wolf1,2, Sina Thusek1,2
1Interdisciplinary Center for Clinical Research Laboratory, Department of Internal Medicine II, Würzburg University Hospital, 97080 Würzburg, Germany.
Abstract:
Invasive fungal infections (IFIs) are difficult to diagnose and to treat and, despite several available antifungal drugs, cause high mortality rates. In the past decades, the incidence of IFIs has continuously increased. More recently, SARS-CoV-2-associated lethal IFIs have been reported worldwide in critically ill patients. Combating IFIs requires a more profound understanding of fungal pathogenicity to facilitate the development of novel antifungal strategies. Animal models are indispensable for studying fungal infections and to develop new antifungals. However, using mammalian animal models faces various hurdles including ethical issues and high costs, which makes large-scale infection experiments extremely challenging. To overcome these limitations, we optimized an invertebrate model and introduced a simple calcofluor white (CW) staining protocol to macroscopically and microscopically monitor disease progression in silkworms (Bombyx mori) infected with the human pathogenic filamentous fungi Aspergillus fumigatus and Lichtheimia corymbifera. This advanced silkworm A. fumigatus infection model could validate knockout mutants with either attenuated, strongly attenuated or unchanged virulence. Finally, CW staining allowed us to efficiently visualize antifungal treatment outcomes in infected silkworms. Conclusively, we here present a powerful animal model combined with a straightforward staining protocol to expedite large-scale in vivo research of fungal pathogenicity and to investigate novel antifungal candidates.
Insights
Researchers developed a novel silkworm model to study invasive fungal infections (IFIs). This cost-effective method uses calcofluor white staining to track disease and evaluate new antifungal treatments, aiding IFI research.
Area of Science:
- Mycology
- Infectious Diseases
- Animal Models
Background:
- Invasive fungal infections (IFIs) present significant diagnostic and therapeutic challenges, leading to high mortality rates.
- The incidence of IFIs has risen, with recent reports linking them to SARS-CoV-2 in critically ill patients.
- Understanding fungal pathogenicity is crucial for developing new antifungal strategies, but mammalian models have limitations.
Purpose of the Study:
- To develop and validate a cost-effective, ethically sound invertebrate animal model for studying IFIs.
- To establish a simple staining protocol for monitoring disease progression and treatment efficacy in vivo.
- To facilitate large-scale research into fungal pathogenicity and the discovery of novel antifungal agents.
Main Methods:
- Optimization of an invertebrate model using silkworms (Bombyx mori).
- Introduction of a calcofluor white (CW) staining protocol for macroscopic and microscopic monitoring.
- Infection of silkworms with human pathogenic fungi, including Aspergillus fumigatus and Lichtheimia corymbifera.
Main Results:
- The silkworm model successfully validated the virulence of A. fumigatus knockout mutants.
- CW staining enabled efficient visualization of disease progression and antifungal treatment outcomes.
- The model demonstrated efficacy in studying fungal pathogenicity and evaluating antifungal candidates.
Conclusions:
- A novel silkworm infection model combined with CW staining provides a powerful tool for in vivo research on fungal pathogenicity.
- This approach overcomes limitations of mammalian models, enabling expedited large-scale studies.
- The model is suitable for investigating novel antifungal candidates and improving the understanding of IFIs.

