Molecular targets for anticandidal chemotherapy

Abstract

A relatively small number of anticandidal chemotherapeutics used in clinical practice is at least in part consequence of a limited number of their molecular targets: ergosterol in the membrane, lanosterol demethylase, b(1!3) glucan synthase, and DNA/RNA biosynthesis. Much more potential novel targets have been revealed by the comparative genomic studies identifying essential genes unique for Candida albicans or resulted from recognition of biomolecules targeted by newly discovered antifungals of natural or synthetic origin. The most promising of them are proteins/enzymes involved in biosynthesis of the cell wall components: chitin synthase, O-mannosyl tranferase, a-1,2 mannosyltransferases, and inositol acylase, in biosynthesis of membrane lipids (Eq. inositolphosphoceramide synthase), in methonine biosynthesis, in translation and posttranslation processing (fungal-specific elongation factors, N-mirystoyl transferase) and in signaling pathways. Target candidates have been also identified among proteins participating in expression of C. albicans virulence factors: filamentation, biofilm formation, and production of secretory hydrolytic enzymes.