Inhibition of pathogenically-related morphologic transition in Candida albicans by disrupting Cdc42 binding to its effectors.

Morphologic transition from the yeast to the hyphal state in Candida albicans is associated with pathogenicity of this human pathogen. Such invasive transition of C. albicans cells is regulated by numerous cell signal transduction pathways, one of which involves a small GTPase, the C. albicans Cdc42 (CaCdcd42), with specific binding to downstream effectors, e.g., CaCla4 and Cst20, containing CRIB domains. Here, we report that in vivo inhibition of CaCdc42 by peptide-mediated transduction of the CRIB polypeptides can inactivate and even reverse the pathogenically related morphologic transition of C. albicans. The current work provides a promising strategy for disease intervention through disrupting protein-protein interactions in signal transduction pathways and brings the concept of signal transduction therapy into the front line of antifungal design as well as therapy for other signal transduction-related diseases.