Caspofungin affects adhesion of Candida to a human cell line

Objective. - Caspofungin is a novel antifungal drug that acts on the fungal cell watt by inhibiting the synthesis of a major component of the cell wall, gtucan. Adhesion of Candida to host tissues is an initial prerequisite of evolution of infection. Interception of adhesion may lead to prevention of infection. Thus, the goal of the present study was to assess the effect of caspofungin at subinhibitory concentrations on the adhesion of C. albicans to a human cell tine, HaCat (Human keratinocytic cell line). Materials and methods. - The adhesion to HaCat cells was carried out in a microtiter system using fluorescent labeled (Fluorescein isothiocyanate -FITC) C. albicans and fluorometric measurements to quantitate the level of adherence. The effect of caspofungin was assessed at subMIC (Minimal. inhibitory concentration) concentrations of 1/4, 1/3, 1/2, and 3/4 MIC in two models: a) as a supplement to the adherence mixture and b) following exposure of the yeasts to the drug for 2 and 3 h prior to the adherence assay. Results. - Caspofungin reduced the level. of adherence by 40 to 90% in comparison to nontreated controls, in aR tested conditions, in dependence of drug concentration and time of exposure. The effect seems not to be associated with the cidal activity of the drug, as the XTT assay and Trypan blue staining showed only a small percentage of nonviable organisms among the caspofungin treated C. albicans. Scanning electron microscopy of C. albicans cultures exposed to caspofungin revealed morphological changes in the treated yeasts that might be associated with the decrease in the adherence level. Conclusion. - The findings of this study reveal that caspofungin at sub-MIC concentrations affects adhesion of C. albicans to human cells, a finding that may be a basis for further investigations, towards the concept of using sub-MIC drug concentrations for prophylaxis in clinical trials. (c) 2007 Elsevier Masson SAS. ALL rights reserved.