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Genetic Pathways Provide new Ways To Combat Candida Infections

Genetic Pathways Provide new Ways To Combat Candida Infections

Gerald R. Fink, et al.

"A new study has uncovered the genetic wiring diagram underlying the infectiousness of Candida albicans, a fungus that causes thrush in babies, vaginal infections in women, and life-threatening infections in chemotherapy and AIDS patients. The study, led by Dr. Gerald R. Fink, Director of the Whitehead Institute for Biomedical Research, reveals that one key to Candida's infectiousness lies in its ability to switch from a rounded form to filamentous forms. Fungal infections in hospitalized patients have almost doubled throughout the 1980s, often with life-threatening results in individuals with weakened immune systems. Candida, in particular, poses a serious threat and is associated with high mortality rates in patients undergoing chemotherapy. Candida is also a major cause of infection in hospitalized patients, especially those in Intensive Care Units, patients after major injuries or surgery, patients with burns, and premature babies.

In this study, Dr. Fink and his colleagues used molecular biology techniques to identify the components of the filamentation circuit in yeast. With the recently completed yeast genome to guide them, the scientists began to knock out suspicious genes and, by a process of elimination, discovered the culprits that are responsible for filamentation. Once scientists identified the key yeast filamentation genes, they simply plucked out the analogous genes in Candida. "Candida albicans is three hundred million years apart evolutionarily from yeast-as far away in evolution as humans are from turtles-and yet, the basic logic circuit was conserved," says Dr. Fink."

But more work needed to be done before scientists could think about reaping the benefits of this remarkable discovery. The key question was whether preventing filamentation in Candida could render the fungus non-infectious. Scientists began to answer this question using macrophages in petri dish, which are normally ineffective against filamentous Candida. When challenged by Candida strains with both pathways knocked out, macrophages emerged victorious. This was good news to researchers, but the real test would come when the Fink lab scientists, in collaboration with scientists at Schering Plough, began experiments with mice.

In general, Candida infections are lethal in mice, and strains with only one filamentation pathway knocked out are still lethal to mice. But when the scientists infected mice with Candida strains with both pathways knocked out, the mice survived and did not succumb to the infection.

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Keywords: Combat Candida Infections Genetic Pathways Candida albicans fungus filamentous form drjefftop advanced

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