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Stopping Pathogenic Fungi

The work by an international collaboration involving IBS and CEA-BIG has led to the discovery of a protein necessary for the survival of pathogenic fungi. Their work could lead to the development of a new antifungal therapeutic strategy.
Published on 16 June 2017

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.

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