ANTIFUNGAL DRUG TARGETS - CANDIDA SECRETED ASPARTYL PROTEASE AND FUNGAL WALL BETA-GLUCAN SYNTHESIS

The incidence of severe, life-threatening fungal infections has increa sed dramatically over the last decade. Unfortunately, in practice the arsenal of antifungal drugs is limited to flucytosine, a few approved azoles, and polyenes, mainly amphotericin B. This situation is rather precarious in view of the extended spectrum of fungi causing severe di sease in immunocompromised patients, development of resistance to some of the currently used agents, and the minimal fungicidal activity of the azoles. Although lagging behind the need for new antifungal agents , the study of fungal biochemistry, physiology, and genetics has under gone a resurgence to new heights of activity, thus providing a framewo rk on which to build drug discovery programs in several new areas, two of which will be discussed in detail: the biology of Candida albicans secreted aspartyl protease with respect to inhibitor discovery, evalu ation, and possible clinical utility; and the fungal cell wall P-gluca ns with respect to the mechanism and regulation of synthesis and targe t sites for drug inhibition.