The abstract of Examining How Changes to the WOR1 Locus or the Wor1 Protein Impact the White-Opaque Switch in Candida albicans”by Peiling He, ScM, Brown University, May, 2024 Candida albicans is a major global health burden, causing over 150 million mucosal infections and approximately 200,000 deaths annually from invasive and disseminated disease, contributing significantly to the 1.6 million lives lost each year due to fungal infections and incurring substantial healthcare costs exceeding $2 billion annually in the USA alone (Richardson, 2022). The high mortality rate of invasive fungal infections, coupled with limited antifungal options and rising resistance, emphasizes urgent need for novel antifungal therapies. Here, we use the white-to-opaque switch in C. albicans as a model to study the epigenetic regulation under different environmental cues, providing insights into phenotypic variation that may impact pathogenicity and could illuminate pathways to develop antifungal therapies. WOR1 is the master regulator of the white-opaque switch, and its expression is critical for formation of the opaque state. This protein contains a large prion-like domain (PrLD), a type of intrinsically disordered region, that is required for Wor1 function and has been shown to promote liquid-liquid phase separation of the protein. The role of the PrLD was further investigated by incorporation of additional copies of the WOR1 PrLD into its sequence and showed that increased PrLD copy number substantially increased Wor1 activity and switching to the opaque state. In a separate line of investigation, we tested how forced expression of WOR1 can drive white-to-opaque switching including the role of the 5’ untranslated region (5’ UTR). We found that even though high levels of Wor1 protein were produced by these WOR1 overexpression assays that white-to-opaque switching was not effective. This potentially suggests that high levels of Wor1 protein are not sufficient to drive switching to the opaque driven process as previously believed. Additional experiments that are now ongoing to further address the mechanism by which WOR1 regulates white-to-opaque switching in C. albicans, and to elucidate the mechanisms that support phenotypic variation in this pathogen.
He, Peiling,
"Examining How Changes to the WOR1 Locus or the Wor1 Protein Impact the White-Opaque Switch in Candida albicans"
(2024).
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:e3jrkrcw/
