School of Plant Science Seminar Series
Morphology of spherules (left) and endospore release (right) of the wild-type and a CPS1 deletion mutant of Coccidioides.
Dr. Marc Orbach
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Abstract: Coccidioides sp., the causative agents of valley fever, are mammalian pathogens endemic to the Southwest US and the Americas. Two-thirds of US infections occur in Arizona. Climate change suggests an expanding range for this pathogen and its disease. To combat this disease, efforts to develop new antifungals or vaccines have been ongoing. Several approaches have been taken to identify fungal virulence factors, including identifying orthologs of virulence genes in other fungal pathogens. We found that the Cochliobolus virulence factor CPS1 was conserved in Coccidioides and expressed early in its parasitic spherule phase. Deletion of CPS1 resulted in a completely avirulent strain, unable to cause disease even in immunodeficient mice. When mice were pre-treated with the delta-cps1 mutant, they were protected against WT Coccidioides infection. This live-attenuated vaccine protects mice and dogs against valley fever and is undergoing regulatory approval for use as a canine vaccine. To understand why the CPS1 deletion is so debilitating to Coccidioides, and support the safety of the vaccine, structural studies of the Cps1 protein and functional and expression studies of CPS1 are being used to define the role of the gene in Coccidioides growth and spherulation.