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Deciphering of Candida parapsilosis induced immune response in Drosophila melanogaster
Katalin Csonka1, Zsolt Tasi1, Viktor Vedelek2
1Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Abstract:
Candida infections are the most prevalent cause of serious human mycoses and are the third most common pathogens isolated from bloodstream infections in hospitalized patients. C. parapsilosis is a member of the non-albicans spp., which have a predilection for causing life-threatening disease in neonates and hospitalized pediatric patients. In this study, we utilized a Drosophila melanogaster infection model to analyze the immunological responses to C. parapsilosis. Our results demonstrate that the Toll pathway in Drosophila controls C. parapsilosis proliferation as the Toll signaling mutant MyD88- flies are highly susceptible to C. parapsilosis. We also confirmed that the MyD88- fly is a convenient invertebrate animal model to analyze virulence properties of different species and strains from the C. parapsilosis sensu lato complex as C. orthopsilosis, C. metapsilosis proved to be less virulent than C. parapsilosis sensu stricto and the N-mannan deficient C. parapsilosis och1Δ/Δ strain showed attenuated pathogenicity in this immunodeficient Drosophila background. We also found that Persephone protease is not required for detection and activation of Toll pathway during C. parapsilosis infection. Furthermore, we observed that Drosophila β-glucan receptor deficient flies where more sensitive to C. parapsilosis compared to wild-type flies; however, we could not find a clear dependence on the recognition of this receptor and the cell wall β-glucan exposure-induced host response. These studies establish this D. melanogaster infection model as an efficient tool in deciphering immune responses to C. parapsilosis as well as for assessing virulence factors produced by this emerging fungal predator.
Insights
The Toll pathway in Drosophila controls Candida parapsilosis proliferation, with MyD88-deficient flies showing high susceptibility. This Drosophila model effectively assesses C. parapsilosis virulence factors and host immune responses.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
- Drosophila melanogaster research model
Background:
- Candida infections are a leading cause of human mycoses and bloodstream infections.
- Candida parapsilosis, a non-albicans species, poses significant threats to neonates and pediatric patients.
- Understanding the host-pathogen interactions and virulence factors of C. parapsilosis is crucial for developing effective treatments.
Purpose of the Study:
- To utilize a Drosophila melanogaster infection model to investigate immunological responses to Candida parapsilosis.
- To analyze the role of the Toll pathway and specific immune receptors in C. parapsilosis infection.
- To evaluate the virulence of different C. parapsilosis species and strains using the established Drosophila model.
Main Methods:
- Infection of wild-type and mutant Drosophila melanogaster strains (MyD88-, Persephone protease-deficient, beta-glucan receptor-deficient) with C. parapsilosis.
- Assessment of fly susceptibility and pathogen proliferation.
- Evaluation of virulence factors, including N-mannan, and host immune pathway activation (Toll pathway).
Main Results:
- The Toll pathway, mediated by MyD88, is critical for controlling C. parapsilosis proliferation, as MyD88-deficient flies exhibit increased susceptibility.
- The Drosophila model successfully differentiated virulence among C. parapsilosis sensu lato complex species (C. orthopsilosis, C. metapsilosis) and strains (N-mannan deficient och1Δ/Δ).
- Persephone protease is not essential for Toll pathway activation during C. parapsilosis infection, and while beta-glucan receptor-deficient flies are more sensitive, a clear dependence on this receptor was not established.
Conclusions:
- The Drosophila melanogaster infection model is an effective tool for studying host immune responses to C. parapsilosis.
- This model aids in deciphering the virulence mechanisms of C. parapsilosis and related species.
- The findings highlight the importance of the Toll pathway in combating C. parapsilosis infections and provide a platform for future virulence factor assessments.
