Candida albicans is the most often cited agent of opportunitistic fungal infections. The incidence of candidal infections have increased substantially over the past decade and concerns over this trend are heightened by the lack of efficacious treatments and high mortality rates. Despite a voluminous literature on C. Albicans, dealing largely with diagnostic techniques and research into its pathogenicity, much of its biology remains hidden. The mechanism(s) of pathogenesis continues to be a topic of conjecture and debate, however, the dimorphic ability of C. Albicans is regarded a significant contributing factor. The investigator previously identified several candidal genes differentially expressed in relation to the dimorphic response. One of these genes, PHR1, is transcriptionally regulated in responses to ambient pH, an environmental signal known to modulate the dimorphic transition of C. Albicans. A second pH-regulated gene, PHR2, encodes a structural and functional homolog of PHR1. Genetic studies have demonstrated that both are required for morphogenesis and virulence and probably encode an essential cell function. Preliminary studies suggest that these genes encode a glycosidase/glycosyl transferase activity that participates in cell wall assembly. While this function is not specific to hypase, the investigator has found a hyphal-specific gene that is dependent upon PHR1 expression. This indicates that the progression of morphogenesis is monitored by the cell and that for some hyphal-specific genes, expression is directly linked to morphogenesis. The investigator has proposed a series of biochemical and genetic experiments to further define the structure and function of the proteins encoded by PHR1 and PHR2 and to define the molecular mechanism(s) that integrate morphogenesis with hyphal-specific gene expression. This information will provide fundamental insights into the process of candidal morphogenesis and will contribute to the investigators long term objective of understanding the molecular basis of dimorphism and its role in pathogenesis.
Showing the most recent 10 out of 16 publications
