A specific inhibitor of keratinolytic proteinase from Candida albicans could inhibit the cell growth of C. albicans.

The authors investigated the influence of culture medium pH and various kinds of protease inhibitors on the growth of Candida albicans when cultivated in liquid medium containing human stratum corneum (HSC) as the nitrogen source. Rapid growth of C. albicans was observed with weakly acidic media, particularly at pH 4.0. From among the various kinds of protease inhibitors added to the media at pH 4.0, pepstatin, a carboxyl protease inhibitor, most strongly inhibited the growth of C. albicans dependent upon its concentration. The antifungal effect of pepstatin was not fungicidal, but was nevertheless effective even at a very low concentration of 0.01 microgram/ml. This inhibitory effect of pepstatin was considerably stronger than that of the well-known antifungal agent, clotrimazole. Pepstatin is a specific inhibitor of keratinolytic proteinase (KPase) from C. albicans; it belongs to the carboxyl proteinases group and has an optimum pH at 4.0. Pepstatin showed a strong antifungal effect, possibly through KPase inhibition, in biologic (HSC) medium that was similar to that encountered in vivo. Our results suggest that KPase may play an important role in the growth of C. albicans and that pepstatin has the possibility of being used as a new type of antifungal agent.