We are studying the function of adhesion to extracellular matrix components in the pathogenesis of Candida albicans. In vitro assays were developed to quantify the adhesion of C. albicans to immobilized fibronectin and its proteolytic and recombinant fragments and to evaluate binding of soluble fibronectin and its fragments to C. albicans in suspension. In contrast to previous publications, we found that high affinity binding is not mediated by the Arg-Gly-Asp recognition sequence and 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. We have identified hemoglobin as a highly specific activator of receptor expression, which reversible induces fibronectin binding when added to defined growth medium. Hemoglobin-inducible binding was observed in all clinical isolates of C. albicans. This activation may play an important role in pathogenesis since only pathogenic strains of C. albicans express hemolytic activity. We are also isolating inhibitors of this activation that may decrease the pathogenicity of C. albicans. We are identifying genes whose expression is regulated by hemoglobin and purifying the receptor mediating inducible binding to fibronectin.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Special Emphasis Panel (LP)
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National Cancer Institute Division of Clinical Sciences
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