Genes Involved in Virulence and Morphogenesis in Candida albicans: the main causative agent of yeast infections

 

Our current research is directed at defining signal transduction pathways involved in pathogenicity and morphogenesis of the opportunistic human pathogen Candida albicans. Candida can colonize mucous membranes causing localized infections or can enter the blood stream causing systemic disease. Both the unicellular yeast form and the filamentous hyphal form of this fungus may be found in infected tissues.

In vitro, ambient temperatures favor the yeast form of C. albicans and physiological temperatures, pH, and serum favor the hyphal form. Pseudohyphae, composed of chains of cells, are also common.

Studies using the S. cerevisiae pheromone response pathway as a tool for isolating C. albicans signal transduction components has led to the identification of C. albicans genes encoding members of a conserved MAP kinase regulatory cascade involved in yeast to hyphal switching ^{1-4 ;11-13;15}.

Lateral hyphal-growth defect from colony borders of null mutants of genes from the C. albicans MAP kinase cascade grown on mannitol at 37°C

These components are homologues of a conserved ERK (extra cellular-regulated-kinase) or MAP (mitogen-activated protein) kinase cascade. Experimental models of Candida infection suggest that this cascade plays a role in infection^1,13,14. Similar elements in the yeast Saccharomyces. cerevisiae are involved in pheromone response, pseudohyphal growth and agar-invasiveness^1,5-8, and in mammalian systems are involved in proliferation and differentiation^9,10.

Some of the genes illustrated above are linked to more information

In addition, we have found that the Candida CaCla4 MEKKK homologue mediates the yeast to hyphal transition in a more general way than the Cst20 MEKKK and promotes fungal infection in an animal model¹⁶. CaCla4 is a homologue of the S. cereivisiae Cla4 gene (a Ste20 MEKKK homologue) which is not involved in the pheromone response pathway.

These studies demonstrate the importance of signal transduction components in the pathogenesis and morphogenesis of fungi. Fungal-specific elements of these cascades should provide fruitful systems for development of novel drug screens. Defining these fungal-specific genes will be a challenge for the future.

Text and figures by Csilla Csank.

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