The Study Of Antifungal Effects Of The Two-component Signal Transduction System Inhibitors Against Candida Albicans In Vitro

ObjectiveTo study antifungal effects of the Two-component Signal Transduction System inhibitors ethacridine and closantel against Candida Albicans in vitro,so as to prepare for the development of a new efficient ,safe and broad-spectrum antifungal.Methods1. the minimum inhibitory concentration(MIC) of f ethacridine and closantel alone was determined against Candida Albicans by N C C L S M 2 7 - A microdilution method; the minimum inhibitory concentration(MIC) of fluconazole was determined respectively when fluconazole combine with ethacridine or closantel against Candida Albicans in the same way.2. The impact of the ethacridine and closantel on the rate of filament was determined respectively by inducing the form of the filament in R P M I - 1640 liquid culture including 10%calf serum.3. Ultrastructure of Candida Albicans exposed to ethacridine and closantel was observed respectively under transmission electron microscope(TEM) and scanning electron microscope (SEM).Results1. Ethacridine and closantel have the characteristic of inhibiting the growth of Candida Albicans . Candida Albicans are hypersensitive to fluconazole with the help of ethacridine or closantel in vitro.2. Closantel could inhibit the hyphal formation in Candida albicans obviously; Ethacridine also could inhibit the hyphal formation in Candida albicans, but Ethacridine could not inhibit the hyphal formation in Candida albicans as obviously as Closantel.3. Defect of the cell wall of the Candida albicans exposed to ethacridine or closantel was found. Under transmission electron microscope,the cells of Candida albicans appeared round,oval or shaped with any budding, the electron dense layer of the cell wall outer was uneven distribution, part of the electron dense layer was lacking, Transparent layer varied in thickness, the cell membrances were tntetrated on the whole ,intracellular vacuoles increased in number. Under scanning electron microscopy, the surface of the cells appeared folding ,cupped and rugged,the budding cells decreased with the bud distributing randomly.ConclusionsTwo-component Signal Transduction System is a new ideal antifungal drug target; Ethacridine and closantel have antifungal properties against Candida Albicans in vitro and they are promising anti-fungal compounds.