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 environmental changes. The dimorphism of C. albicans plays an important role 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 sulphydryl groups(s) containing components(s) in the yeast-to-mycelium transition of C. albicans, we examined the effect of a group of newly synthesized thiol-alkylators on the production of germ tubes from yeast cells. Several conjugated styryl ketones which are thiol-alkylators, and p-chloromercuriphenylsulphonate (a known non-penetrating thiol-blocker) inhibited the yeast-to-mycelium conversion of C. albicans. The thiol-alkylators at 20 μM failed to inhibit four key enzymes (γ-glutamyltranspeptidase, glutathione reductase, glutathione S-transferase and glutathione peroxidase) involved in glutathione utilization indicating that the inhibition of yeast-to-mycelium conversion is not mediated by the inhibition of glutathione metabolic enzymes. Moreover, these results suggest that a key thiol-blocker sensitive component(s) containing critical sulphydryl group(s) is involved in the yeast-to-mycelium transition of C. albicans.