Candida albicans is an opportunistic fungal pathogen that is typically a commensal organism in the human GI tract, mouth, and skin. Under certain conditions, particularly in those that are immunocompromised, infections caused by Candida species can become systemic and have a 30-60% mortality rate. Fluconazole is routinely used to treat candidiasis and works by directly inhibiting the heme protein lanosterol 14-a-demethylase (CYP51). This blocks the ergosterol biosynthetic pathway leading to a buildup of toxic sterols in the plasma membrane. One consequence of fluconazole’s mechanism of action is a change in how C. albicans uses, stores, and transports transition metals such as Cu, Fe, Mn, and Zn. Our study aims to examine these changes with and without Cu present, as additive Cu decreases trailing growth of cells treated with fluconazole. We have used size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICP-MS) in combination with bulk proteomics to determine if proteins are properly metallated due to treatment and if there is a change in protein abundance. Preliminary results indicate changes in C. albicans’ metalloproteome overtime. Overall, our research will give a more detailed view on how fungi react to azole treatment. In addition, this work may elucidate specific proteins to target in combination with fluconazole treatment to further shift C. albicans’ metallohomeostasis and develop more effective antifungal drugs.

Changes to Candida albicans' metalloproteome as a result of azole drug stress

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.