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.
The proposed research project Cell Wall Biogenesis in Candida albicans includes a series of experiments to characterize a key step in the formation of the cell wall of the human pathogenic fungus Candida albicans, which can cause invasive infections in patients with compromised immune systems. The particular step in cell wall biosynthesis that will be studied in the proposed research project, the incorporation of protein into the cell wall, is a newly discovered step in formation of the cell wall. The cell wall is vita to the survival of the fungus, and agents that disrupt cell wall formation would be excellent targets for the development of antifungal agents for the treatment of invasive fungal infections.
| Ao, Jie; Free, Stephen J (2017) Genetic and biochemical characterization of the GH72 family of cell wall transglycosylases in Neurospora crassa. Fungal Genet Biol 101:46-54 |
| Liu, Longzhou; Free, Stephen J (2016) Characterization of the Sclerotinia sclerotiorum cell wall proteome. Mol Plant Pathol 17:985-95 |
| Ao, Jie; Aldabbous, Mash'el; Notaro, Marysa J et al. (2016) A proteomic and genetic analysis of the Neurospora crassa conidia cell wall proteins identifies two glycosyl hydrolases involved in cell wall remodeling. Fungal Genet Biol 94:47-53 |
| Fu, Ci; Sokolow, Eleanor; Rupert, Christopher B et al. (2014) The Neurospora crassa CPS-1 polysaccharide synthase functions in cell wall biosynthesis. Fungal Genet Biol 69:23-30 |
