We are studying the function of adhesion to extracellular matrix components in the pathogenesis of Candida albicans. Using in vitro assays to quantify adhesion of C. albicans to immobilized fibronectin and its proteolytic and recombinant fragments and to evaluate binding of soluble fibronectin to C. albicans in suspension, we found that interactions of fibronectin with this organism are not mediated by the Arg-Gly-Asp integrin recognition sequence of fibronectin. High affinity binding, observed following grown in complex medium, is primarily mediated by the collagen-binding domain of fibronectin. A 30 kDa fragment of fibronectin containing the collagen binding domain is as active as intact fibronectin for binding to C. albicans. Expression of fibronectin receptors is tightly regulated by growth conditions. C. albicans grown in defined media do not bind fibronectin. We have identified hemoglobin as a highly specific activator of receptor expression, which reversible induces fibronectin binding when added to defined growth medium. This binding is of lower affinity and is mediated by the cell-binding domain of fibronectin. Hemoglobin- inducible binding was observed in all clinical isolates of C. albicans and in other members of the Candida genus. This activation may play an important role in pathogenesis, since only pathogenic strains of C. albicans express hemolytic activity. Inhibitors of this activation process may decrease the pathogenicity of C. albicans. We have identified ESTs for several genes whose expression is induced by hemoglobin and a 55 kDa receptor that mediates inducible binding to fibronectin. - Candida albicans, infection, adhesion molecules, signal transduction,

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC009173-11
Application #
6290802
Study Section
Special Emphasis Panel (LP)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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