Chapter 4 : Candida albicans Hypha Formation and Virulence

Abstract:

Current research shows that major changes in gene expression accompany morphogenesis and suggest that fungal attributes necessary for proliferation and survival in the host are present in both yeast and hyphal growth forms. Manipulation of host-fungus interactions in animal models has provided insight into the role of hypha formation in virulence. The use of genetic manipulation has led to the discovery that transcription factors and signal transduction pathways are critical for the proper regulation of morphogenic conversions in Candida albicans. Mutant strains of C. albicans that are defective in hypha production in host tissue have reduced virulence in murine models of systemic candidiasis. A caveat associated with the use of morphogenic mutants in attempts to understand the role of hypha formation in virulence is that the roles of apical and budding modes of growth cannot be separated from morphology-specific gene expression. Studies of mutants displaying defects in hypha-specific gene expression but not in hypha production support the principle that the role of hyphae in virulence is more closely related to the changes in gene expression profiles that accompany hyphal growth than to hyphal growth itself. In addition to HWP1, PLD1, and other potential virulence factors, genes that could potentially regulate virulence factor gene expression during hypha production, such as those encoding transcription factors, signal transduction components, and proteins that function in secretion, as well as others, were identified.