Intracellular and Extracellular Aspartic Proteinases of Pathogenic Candida Species: Can their Inhibitors be Further Developed?

Abstract

Pathogenic yeasts of the genus Candida represent a serious threat to immunocompromised individuals. Soluble secreted aspartic proteinases produced by these opportunistic pathogens have been studied as one of the virulence factors and potential target for therapeutic intervention. Several structures of these enzymes in complex with inhibitors have been published; however, only a limited number of novel inhibitory compounds have been reported recently. Other members of aspartic proteinase family received less attention, although they are important for Candida survival in the host environment. Proteinases attached to the cell surface by GPI-anchor, as well as vacuolar aspartic proteinases may thus become promising therapeutic targets. This review summarizes the data available on less studied aspartic proteinases of C. albicans, and poses the question, whether the knowledge of vacuolar and GPI-anchored aspartic proteinases from Saccharomyces cerevisiae can inspire design of compounds inhibiting these types of enzymes in the pathogenic yeasts. Keywords: Aspartic proteinase, Candida spp, GPI-anchored protein, IA3, Saccharomyces cerevisiae, secreted proteinase, vacuole, virulence factors, antimycotics, mycoses