The present study indicates that the direct interaction between 5-HT and C. albicans affects fungal virulence properties such as hyphal elongation, extracellular phospholipase activity and Sap production.
Hyphal elongation of C. albicans
was altered significantly (P
< 0.05) at 14.7–3.7 mM 5-HT. The phenomenon of dimorphism by C. albicans
is an important virulence factor [10
]. It is widely recognised that formation of hyphae enhances adherence and tissue invasion, and the transition from conidia to hyphae supports invasive fungal diseases [11
]. Hyphal elongation of 5-HT-treated fungus was more prominent at 37 °C compared with 30 °C.
In addition, concentrations of 14.7–1.8 mM 5-HT decreased phospholipase activity without showing an impairment of fungal growth. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi such as C. albicans
has recently gained credence. Extracellular phospholipase activity has been shown to be predictive for mortality in a murine mouse model of disseminated candidiasis, and increased phospholipase activity has been correlated with increased mucosal pathogenicity in this opportunistic yeast [12
]. Phospholipase secretion is also not limited to one fungal genus [12
]. The virulence of C. albicans
is defined by the production of proteinases such as Saps and phospholipases [9
]. These hydrolytic enzymes destroy or derange constituents of host cell membranes, leading to physical disruption and/or membrane dysfunction [14
The highest reduction in Saps was found at 7.3–1.8 mM 5-HT, concentrations that did not affect the growth of C. albicans
. The majority of Sap proteins are secreted by those C. albicans
cells that directly adhere to the epithelial surface [15
]. A dominant Sap isoenzyme in vitro and possibly in vivo is Sap2, which is the predominant isoenzyme investigated here [9
In addition to being fungicidal at higher concentrations, 5-HT exerts an inhibitory effect on C. albicans even at concentrations that are up to one magnitude lower, by inhibiting phospholipase activity and Sap2 production.
The mechanism by which 5-HT acts on C. albicans
is not yet known. The role of 5-HT in antifungal host defence needs to be clarified in more detail as there is a surprising coincidence of an increased rate of infections and low 5-HT concentrations such as in Down’s syndrome [17
] and AIDS [18
]. Thrombocytes are able to store up to 65 mM 5-HT within the dense granules [4
In conclusion, our findings show that 5-HT treatment of C. albicans affected hyphal elongation, phospholipase activity and production of Saps.
The data encourage us to define the role of 5-HT in antifungal host defence. It could be of great help to identify the mode of action in order to develop and research new antifungal agents.