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. When the wiring diagram underlying this switch is inactivated, Candida infections are no longer deadly in mice.
The implications of these results for humans are enormous, given that current treatment options for invasive fungal infections are seriously limited. "If we could design drugs that inactivate or block Candida's filamentation pathways, we might be able to fight the organism's insidious and devastating effects on patients with weak immune systems," says Dr. Fink. "Our study also shows that this genetic pathway is a common theme among fungal pathogens and so may provide important insights on how plant and animal pathogens work."
The results are reported in the September 5 issue of the journal Cell by first author Hsiu-Jung Lo and her colleagues from Dr. Fink's lab, Children's Hospital in Boston, MA, and Schering-Plough Research Institute in Kenilworth, NJ.
Using state of the art videomicroscopy techniques, Dr. Fink and his associates recently captured on video the fate of immune cells infected with Candida in a petri dish. When Candida enters a host, the organism is eaten up by cells called macrophages, which are the sentinels of the immune system. But soon, the fungi fight back, switching to a filamentous form and tearing through the macrophage walls, destroying them. Fortunately, in people with healthy bone marrow, other immune system cells called neutrophils come to the rescue to destroy the filamentous Candida. However in patients with weakened immune systems, who lack healthy b
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Contact: Seema Kumar or Eve Nichols
kumar@wi.mit.edu
(617) 258-5183
Whitehead Institute for Biomedical Research
4-Sep-1997