Cell Wall Biogenesis in Candida albicans

DESCRIPTION (provided by applicant): The formation of the cell wall is a critical for the survival of Candida albicans and other fungal pathogens. Recent research advances in non-pathogenic fungi have demonstrated that a particular group of cross-linking enzymes can function to cross-link cell wall proteins into the cell wall. These cross-linking enzymes recognize oligosaccharides present on cell wall proteins and incorporate these oligosaccharides into the cell wall glucan/chitin matrix. The proteins are incorporated into the wall as part of this process The incorporation of cell wall proteins into the cell wall is a critical step in cell wall biogeness. The proposed pilot study will demonstrate that these cross-linking enzymes function in the cross-linking of cell wall proteins into the cell wall of C. albicans. The pilot study will also characterize the substrate specificity of the C. albicans cross-linking enzymes. Elements of the oligosaccharides present on the cell wall protein and elements of the glucan/chitin matrix must be recognized as substrates in order for the enzyme to cross-link the protein into the wall. The pilot study will help identify what specific characteristics of the oligosaccharides are important for the cross-linking reaction. The research will also determine what elements in the glucan/chitin matrix are used by the enzyme. An understanding of the cross-linking enzymes' substrate requirements will play a key role in the development of antifungal agents that act as inhibitors of these cross-linking enzymes. Relevance: Candida albicans is an important human pathogenic fungus. Invasive infections by C. albicans and other fungal pathogens are a major health concern for immunocompromised patients. Such infections are difficult to treat and have a high mortality rate. The proposed pilot study will examine whether a newly discovered group of enzymes that have been shown to function in the biogenesis of the fungal cell wall in non-pathogenic fungi, are critical for the growth and survival of C. albicans. A demonstration that these enzymes are needed for cell wall biosynthesis in C. albicans will highlight the possibility o targeting these enzymes for the development of an antifungal agent to treat invasive Candidiasis and other invasive fungal infections.