Authors:

Laila Fortson

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About Paper:

Fungal infections in humans have historically been overlooked in disease research, however, they result in over 1.5 million deaths annually. Candida albicans, according to The World Health Organization, is one of four critical priority fungal pathogen species, posing a major threat to individuals. They can enter the bloodstream and invade internal organs, causing death in immunocompromised patients. Few medicines exist to treat fungal infections such as these. To address this, my project's focus is to develop and validate the auxin inducible degradation (AID) system in fungal pathogens, specifically Candida albicans, for anti-fungal drug discovery. The AID system is an effective functional genomics tool used for protein characterization. It provides rapid degradation of a protein of interest after adding the plant hormone auxin. We hypothesize that AID can also be used in the context of invasive fungal infection models to identify new anti-fungal drug targets. In this context, auxin is a surrogate for a "drug" against the target protein. C. albicans depends on hyphal growth to invade mammalian tissue for infection. The HGC1 gene is expressed in hyphae, and it is essential both for hyphal formation and infection. Hence, we are targeting HGC1 with the AID system to induce protein degradation in genetically manipulated strains of C. albicans. Initially, I confirmed that HGC1-AID strains could form hyphae in the presence of auxin normally using microscopy. I am currently testing if auxin-induced HGC1 degradation can block an invasive infection in Galleria mellonella larvae, a simple and common invertebrate infection model for Candida albicans. If successful, then AID can be used to broadly test if degradation of other proteins is sufficient to block infections and thereby identify potential new anti-fungal targets. Keywords: AID; Candida albicans; Fungal Pathogens; Protein Degradation

Source:

Purdue University / 2024

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Co-authors:

Laila Fortson