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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Antiphagocytic protein 1 increases the susceptibility of Cryptococcus neoformans to amphotericin B and fluconazole
Muhammad Ghaffar1, Cody Orr1, Ginny Webb1
1Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, South Carolina, United States of America.
Abstract:
Cryptococcus neoformans is a facultative intracellular pathogen responsible for the most common cause of fungal meningioencephalitis, occurring primarily in immunocompromised individuals. Antiphagocytic protein 1 (App1) is a virulence factor produced by C. neoformans that inhibits phagocytosis of the yeast by host macrophages. Treatment of cryptococcosis includes amphotericin B, fluconazole, and flucytosine. Virulence factors have been shown to affect the susceptibility of the pathogen to antifungal drugs. In this study, we aimed to examine the relationship between App1 and antifungal drugs. We found that short-term exposure to amphotericin B downregulates APP1 expression while exposure to fluconazole upregulates APP1. In addition, App1 was found to increase the susceptibility of the yeast to amphotericin B and fluconazole. This study provides evidence of an intricate relationship between App1 and antifungal drugs.
Insights
Cryptococcus neoformans virulence factor App1 (Antiphagocytic protein 1) impacts antifungal drug effectiveness. App1 increases susceptibility to amphotericin B and fluconazole, revealing a complex drug-pathogen interaction.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Cryptococcus neoformans causes fungal meningoencephalitis, primarily in immunocompromised individuals.
- Antiphagocytic protein 1 (App1) is a C. neoformans virulence factor inhibiting macrophage phagocytosis.
- Standard treatments for cryptococcosis include amphotericin B, fluconazole, and flucytosine.
Purpose of the Study:
- To investigate the relationship between the C. neoformans virulence factor App1 and antifungal drug susceptibility.
- To determine how App1 expression is affected by common antifungal agents.
Main Methods:
- Quantitative analysis of APP1 gene expression in C. neoformans.
- Exposure of C. neoformans to amphotericin B and fluconazole.
- Assessment of yeast susceptibility to antifungal drugs in the presence and absence of App1 modulation.
Main Results:
- Short-term exposure to amphotericin B downregulated APP1 expression.
- Exposure to fluconazole upregulated APP1 expression.
- App1 significantly increased the susceptibility of C. neoformans to both amphotericin B and fluconazole.
Conclusions:
- App1 plays a crucial role in modulating the susceptibility of C. neoformans to key antifungal drugs.
- The interplay between App1 and antifungal agents suggests potential therapeutic strategies targeting virulence factors.
- Understanding this intricate relationship is vital for optimizing cryptococcosis treatment.
