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Electrophysiological Recording of The Central Nervous System Activity of Third-Instar Drosophila Melanogaster
Published on: November 21, 2018
Drosophila melanogaster as a model to study virulence and azole treatment of the emerging pathogen Candida auris
Sebastian Wurster1, Ashwini Bandi1, Nicholas D Beyda2
1Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Objectives:
Candida auris is an emerging, often MDR, yeast pathogen. Efficient animal models are needed to study its pathogenicity and treatment. Therefore, we developed a C. auris fruit fly infection model.
Methods:
TollI-RXA/Tollr632 female flies were infected with 10 different C. auris strains from the CDC Antimicrobial Resistance bank panel. We used three clinical Candida albicans strains as controls. For drug protection assays, fly survival was assessed along with measurement of fungal burden (cfu/g tissue) and histopathology in C. auris-infected flies fed with fluconazole- or posaconazole-containing food.
Results:
Despite slower in vitro growth, all 10 C. auris isolates caused significantly greater mortality than C. albicans in infected flies, with >80% of C. auris-infected flies dying by day 7 post-infection (versus 67% with C. albicans, P < 0.001-0.005). Comparison of C. auris isolates from different geographical clades revealed more rapid in vitro growth of South American isolates and greater virulence in infected flies, whereas the aggregative capacity of C. auris strains had minimal impact on their growth and pathogenicity. Survival protection and decreased fungal burden of fluconazole- or posaconazole-fed flies infected with two C. auris strains were in line with the isolates' disparate in vitro azole susceptibility. High reproducibility of survival curves for both non-treated and antifungal-treated infected flies was seen, with coefficients of variation of 0.00-0.31 for 7 day mortality.
Conclusions:
Toll-deficient flies could provide a fast, reliable and inexpensive model to study pathogenesis and drug activity in C. auris candidiasis.
Insights
A new fruit fly model effectively studies Candida auris, an emerging yeast pathogen. This model shows C. auris is more deadly than C. albicans and helps test antifungal drugs.
Area of Science:
- Mycology
- Infectious Diseases
- Model Organisms
Background:
- Candida auris is an emerging multidrug-resistant (MDR) yeast pathogen.
- Efficient animal models are crucial for understanding C. auris pathogenicity and evaluating treatments.
- Existing models may not fully capture the challenges posed by this resilient fungus.
Purpose of the Study:
- To develop and validate a novel fruit fly (Drosophila melanogaster) infection model for Candida auris.
- To compare the virulence of C. auris strains against a control pathogen, Candida albicans.
- To assess the efficacy of antifungal drugs (fluconazole, posaconazole) in the established fly model.
Main Methods:
- Infection of Toll-deficient female flies (TollI-RXA/Tollr632) with ten C. auris strains and three C. albicans strains.
- Assessment of fly survival rates, fungal burden (colony-forming units per gram of tissue), and histopathology.
- Evaluation of drug protection assays using fluconazole- or posaconazole-containing food.
Main Results:
- All ten C. auris strains demonstrated significantly higher mortality rates in flies compared to C. albicans.
- South American C. auris isolates exhibited faster in vitro growth and greater virulence in the fly model.
- Antifungal treatment (fluconazole, posaconazole) reduced fungal burden and improved survival, correlating with in vitro susceptibility.
- The model showed high reproducibility in survival curves for both treated and untreated infected flies.
Conclusions:
- Toll-deficient fruit flies provide a rapid, reliable, and cost-effective model for studying C. auris pathogenesis.
- This model is suitable for evaluating the activity of antifungal agents against C. auris infections.
- The developed model aids in understanding the complex interactions between C. auris and its host.
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