Farnesol, a Fungal Quorum-Sensing Molecule Triggers Candida Albicans Morphological Changes by Downregulating the Expression of Different Secreted Aspartyl Proteinase Genes

Nadege Decanis

doi:10.2174/1874285801105010119

Abstract

The aim of this study was to determine the effect of exogenous farnesol in yeast-to-hyphae morphogenesis, and Saps (2, 4, 5 and 6) mRNA expressions by a Candida strain that does not produce endogenous farnesol. C. albicans was cultured in the absence and presence of farnesol at various concentrations (10, 100, and 300 µM), in proteinase induction medium, and then used to determine yeast-to- hyphae changes, Candida ultrastructure and to determine Saps 2, 4, 5 and 6 expressions using q-TR-PCR and ELISA (for Sap2). Data demonstrated that farnesol greatly reduced the yeast-to-hyphae morphogenesis of a Candida strain that does not produce endogenous farnesol. Farnesol induced several ultrastructural alterations, including changes in the cell-wall shape, a visible disconnection between the cell wall and cytoplasm with an electron-lucent zone between them, and the presence of electron-dense vacuoles. Tested on gene expressions, farnesol was able to significantly (p < 0.01) decrease Sap2 secretion and mRNA expression. Farnesol downregulated also Sap4-6 mRNA expression. These results demonstrated for the first time that farnesol modules Candida morphogenesis through a downregulation of Saps 2, 4, 5 and 6 expressions. Overall these data point to the potential use of farnesol as an antifungal molecule

Highlights

Candida is a fungus, which accounts for nearly 96% of all opportunistic mycoses and is the fourth most common bloodstream pathogen in North American and seventh in European hospitals [1, 2]
In an experimental protocol that induce hyphae formation through the presence of BSA in the culture medium, we showed that farnesol reduced, up to 10-fold, the Candida transition from yeast to hyphal forms
Studies have shown that farnesol produced in situ by planktonic C. albicans cultures prevented biofilm formation [30]

Summary

Introduction

Candida is a fungus, which accounts for nearly 96% of all opportunistic mycoses and is the fourth most common bloodstream pathogen in North American and seventh in European hospitals [1, 2]. Candida infections lead to a prolonged stays in intensive care unit and hospital which causes significant health and economic problems [5, 6]. Among the Candida genus, Candida albicans is a fungal organism that forms part of the normal oral microbial flora in approximately 50% of healthy individuals [7]. C. albicans is a polymorphic organism and can grow as yeast, pseudohyphae or hyphae; each differing in its morphology and virulence [8]. The yeast form is commonly associated with the commensal

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