An estimated 2 million people worldwide have invasive fungal infections
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Every year, an estimated 2 million people worldwide suffer from invasive fungal infections and nearly 800,000 deaths – but a team of international scientists has discovered a new antifungal treatment.
Researchers from the University of Southern California and France found that Bdf1 is a gene regulatory protein that is critical for the survival of the pathogenic fungus Candida albicans.
"We have demonstrated that Bdf1 is an important new goal for drug design," said Charles McKenna, a senior author of the study and professor of chemistry and pharmaceutical science at the University of Southern California at Los Angeles. "Our results suggest that compounds that bind to this target can disrupt the growth of fungi and open the way for new drug treatments for fungal diseases."
The French scientist who led McKenna's research is Jérôme Govin and Carlo Petosa from the Alpine University of Grenoble.
The fungus Candida albicans is an invasive pathogen that is normally controlled by the immune system in healthy people. However, people with weaker immune systems, including those with cancer, HIV or autoimmune diseases, are susceptible to infection, which can be life-threatening, McKenna said.
The team's findings were published in the journal Nature Communications on May 18 and may be timely. Fungal infections such as candidiasis are increasingly resistant to drug treatment. According to the US Centers for Disease Control and Prevention, approximately 46,000 American patients are infected with invasive candidiasis each year.
“When a susceptible population develops a Candida infection, the fungus may enter the bloodstream. If the treatment is unsuccessful, its mortality rate is very high – in the 40% range,” McKenna said. “Our drug count is very limited and can effectively treat this systemic infection. Unfortunately, like many other pathogens, Candida albicans is increasingly resistant to a few available drugs, increasing patient bets and urgently needed Take a new approach."
Convergent biological science research
McKenna pointed out that his team's discovery was achieved through the integration of biological sciences, an emerging multidisciplinary research fusion designed to accelerate health-related discoveries from the laboratory to the bedside. Drawing on experience from a diverse network of scientists, engineers and students, the University of Southern California's Michelson Convergence Bioscience Center plans to promote biomedical discovery, innovative and real-world solutions for rapid detection and treatment from microbial infections to Alzheim Diseases such as Mohs disease and cancer.
This fall, the University of Southern California will open the center of this new program, Michelson Hall, a 190,000-square-foot high-tech research facility that is donated by retired spine surgeon Gary K. Michelson and his wife, Alya Michelson, for $50 million. . The facility will house the new USC Drug Discovery Center, with McKenna as its director.
Many scientists are investigating alternatives to diseases such as cancer by manipulating gene expression. The USC-Grenoble team was the first team to demonstrate that this method can be used to target fungal infections.
"The idea is that if you turn off this particular protein, Bdf1, you completely destroy the entire process of gene expression, and fungi can't grow," Govin said. "In addition, when injected into mice, the fungus is no longer toxic."
The challenge for scientists is to find a compound that shuts down the Bdf1 protein without erroneously affecting any similar protein in humans.
"Using a technique called X-ray crystallography, we found that the fungal Bdf1 protein and the corresponding human protein are very different at the atomic level," Petosa said. "This suggests that compounds can specifically inhibit fungal proteins without affecting human bromodomain proteins."