DURHAM, N.C. Molecular biologists in the Mycology Research Unit at Duke University Medical Center have traced cellular pathways that are targeted to enhance the action of drugs used to treat fungal infections in people with compromised immune systems, such as those undergoing organ and bone marrow transplants. The discovery of how the immune-suppressing drugs enhance the action of antifungal drugs could lead to the development of new drugs designed to treat fungal infections such as systemic yeast infections and often-deadly cryptococcal infections.
Led by Dr. Joseph Heitman, who is a Howard Hughes Medical Institute investigator at Duke, the research team explored the mechanism behind the effectiveness of administering the azole class of antifungal drugs such as fluconazole (Diflucan), with cyclosporin or FK506, two drugs commonly used to suppress rejection of transplanted organs and tissues.
The study is published in the Feb. 15 issue of the EMBO Journal, a journal published by the European Molecular Biology Organization.
Cyclosporin and FK506 block rejection of transplanted organs by inhibiting immune-system signaling pathways that activate T-cells. These drugs block calcineurin, an enzyme that plays a critical role in activating immune cells. Suppression of the immune system is necessary for transplanted organs to survive, but renders patients susceptible to infections by bacteria, viruses and fungi.
"The azoles are very nontoxic in humans, but the problem is they don't kill fungal cells. Instead, these drugs act by inhibiting fungal cell growth. The cells stop growing, but they don't die. As a result, a lot of fungal isolates become resistant to the azoles," Heitman said.
The study was funded by grants from the National Institute of Allergy and Infectious Diseases.
Unlike bacteria or viruses, fungi are eukaryotic cells that resemble cells of the human body. Fungal infections can thus be difficult to treat, Heitman s
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Contact: Amy Reyes
a.reyes@duke.edu
919-684-4148
Duke University Medical Center
6-Feb-2002