INHIBITION OF YEAST-TO-MYCELIUM CONVERSION OF CANDIDA-ALBICANS BY CONJUGATED STYRYL KETONES

Candida albicans is a dimorphic pathogenic yeast capable of producing alternate morphological forms (yeast or mycelium) in response to envir onmental changes. The dimorphism of C. albicans plays an important rol e in the pathophysiology of this organism. The intracellular level of glutathione, which helps to maintain the oxidation-reduction potential of the cell, is decreased significantly during the yeast-to-mycelium conversion implicating the possible involvement of thiols in the yeast -to-mycelium transition. To evaluate the possible participation of sul phydryl group(s) containing component(s) in the yeast-to-mycelium tran sition of C. albicans, we examined the effect of a group of newly synt hesized thiol-alkylators on the production of germ tubes from yeast ce lls. Several conjugated styryl ketones which are thiol-alkylators, and p-chloromercuriphenylsulphonate (a known nonpenetrating thiol-blocker ) inhibited the yeast-to-mycelium conversion of C. albicans. The thiol -alkylators at 20 mu M failed to inhibit four key enzymes (gamma-gluta myltranspeptidase, glutathione reductase, glutathione S-transferase an d glutathione peroxidase) involved in glutathione utilization indicati ng that the inhibition of yeast-to-mycelium conversion is not mediated by the inhibition of glutathione metabolic enzymes. Moreover, these r esults suggest that a key thiol-blocker sensitive component(s) contain ing a critical sulphydryl group(s) is involved in the yeast-to-myceliu m transition of C. albicans.