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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Effect of fluconazole on human polymorphonuclear leucocyte functions ex vivo against Candida albicans
U S Gürer1, A Cevikbaş, C Johansson
1Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Marmara, Haydarpaşa, Istanbul, Turkey.
Abstract:
Polymorphonuclear leucocytes (PMNs) are important components of host defence against fungi. We investigated the ex vivo effect of fluconazole on chemotaxis, adherence, superoxide anion (O-2) generation and intracellular killing of Candida albicans blastoconidia after the administration of fluconazole (300 mg per os) to healthy volunteers. With regard to chemotaxis in response to zymosan-activated serum (ZAS), as measured using an agarose gel technique, fluconazole neither increased, nor decreased the chemotaxis of PMNs. The adherence was significantly enhanced after exposure of PMNs to fluconazole under ex vivo conditions, whereas, O-2 production after stimulation of PMNs with ZAS was not affected by fluconazole. The effect of fluconazole on intracellular killing of C. albicans blastoconidia by PMNs was determined by viable colony count, after release of yeast cells from disturbed neutrophils. Fluconazole under in vitro conditions, at a therapeutic concentration, significantly increased the intracellular killing of C. albicans by PMNs at 30 min when compared with the results obtained in ex vivo experiments (p < 0.001). During 90 min of exposure, no significant difference was found between in vitro and ex vivo conditions (p > 0.05).
Insights
Fluconazole enhances polymorphonuclear leucocyte (PMN) adherence and intracellular killing of Candida albicans. This antifungal medication did not affect PMN chemotaxis or superoxide anion generation in healthy volunteers.
Area of Science:
- Mycology
- Immunology
- Pharmacology
Background:
- Polymorphonuclear leucocytes (PMNs) are crucial for host defense against fungal infections.
- Understanding the impact of antifungal agents on immune cell function is vital for optimizing treatment strategies.
Purpose of the Study:
- To evaluate the ex vivo effects of a single oral dose of fluconazole (300 mg) on human PMN functions.
- To assess fluconazole's impact on PMN chemotaxis, adherence, superoxide anion generation, and intracellular killing of Candida albicans.
Main Methods:
- Healthy volunteers received oral fluconazole (300 mg).
- Ex vivo analysis of PMN chemotaxis (zymosan-activated serum), adherence, and superoxide anion (O-2) generation.
- Intracellular killing of Candida albicans blastoconidia by PMNs was assessed using viable colony counts.
Main Results:
- Fluconazole did not alter PMN chemotaxis or O-2 generation.
- Significant enhancement of PMN adherence was observed ex vivo.
- In vitro, therapeutic concentrations of fluconazole significantly increased intracellular killing of C. albicans by PMNs at 30 minutes compared to ex vivo conditions.
Conclusions:
- Fluconazole administration enhances PMN adherence and improves the intracellular killing capacity against Candida albicans, particularly in vitro.
- These findings suggest that fluconazole may augment host immune responses against fungal pathogens.

