Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Infectious diseases | DNA | Structural biology
Pathogenic fungi are responsible for generalized infections in 2 million patients every year and lead to 800,000 deaths. Immunocompromised individuals are particularly susceptible to these infections such as patients with AIDS, cancer patients treated with chemotherapy, and patients who received organ transplants or stem cells. The only drug options available to hospitals are four classes of antifungal molecules, whose massive use in an increasing number of patients at risk has led to the emergence of resistant strains, posing an urgent need for new antifungal therapeutic strategies.
A consortium of researchers from IBS, CEA-BIG, Institut Pasteur and the University of Southern California has closely studied the Bdf1 protein, which is part of a family of proteins in both humans and yeast that is highly conserved during evolution. These BET proteins regulate the expression of genes by binding to chromatin, a structure that organizes the DNA chain in the genome. Molecules have recently been developed to inhibit the action of human BET proteins, capable of drastically deregulating the gene expression program. These inhibitors have a wide therapeutic potential: their efficiency is being tested in several clinical trials for the treatment of cancer, diabetes, inflammatory and cardiovascular diseases.
In this context, the Franco-American consortium has focused on protein BET Bdf1, not in humans, but in the pathogenic fungus Candida albicans. This fungus is responsible for generalized infections in 0.3% of hospital admissions in France, and is fatal in 40% of infected patients. The scientists have shown that this protein of interest is essential for the survival and virulence of Candida albicans. They analyzed the atomic structure of the two domains of Bdf1 binding to chromatin, and used their structural specificity to find selective inhibitors, distinct from those targeting human proteins. Their work paves the way to the development of a new antifungal therapeutic strategy.
Selective BET bromodomain inhibition as an anti-fungal therapeutic strategy | Nature Communications
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.