Every year, fungal infections caused by Candida yeast claim hundreds of thousands of lives worldwide. As antifungal resistance continues to rise, current treatments are becoming less effective, making the search for new therapeutic strategies increasingly urgent. One promising approach targets Bdf1, a fungal protein that plays a key role in gene regulation and is essential for Candida viability. However, developing a Bdf1 inhibitor that selectively targets the fungal protein without affecting its human counterparts, while also demonstrating its on-target activity inside the fungal cell, poses a significant challenge.
To overcome this hurdle, researchers at the IBS, in collaboration with the Institute for Advanced Biosciences, CHU Grenoble Alpes, the University of Rennes, and the University of Southern California, have developed novel experimental tools. They engineered "humanized" Candida strains, replacing the targeted domains of Bdf1 with their human equivalents, and designed a luminescence-based proximity assay to measure the interaction of Bdf1 with chromatin. Using these tools, they identified a Bdf1 inhibitor that is effective against multiple Candida species, including drug-resistant strains, and confirmed its antifungal activity in a preclinical infection model.
This research provides essential proof of concept and paves the way for the development of a new class of antifungal drugs.
Humanized Candida and NanoBiT assays expedite discovery of Bdf1 bromodomain inhibitors with antifungal potential. Wei K, Arlotto M, Overhulse JM, Dinh T-A, Zhou Y, Dupper NJ, Yang J, Kashemirov BA, Dawi H, Garnaud C, Bourgine G, Mietton F, Champleboux M, Larabi A, Hayat Y, Indorato RL, Noirclerc-Savoye M, Skoufias D, Cornet M, Rabut G, McKenna CE, Petosa C, Govin J. Advanced Science 2025 ; e2404260
Contact : Carlo Petosa (IBS/Epigenetics and molecular pathways Group)