""""""""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.""""""""

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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Navarathna, Dhammika H; Roberts, David D; Munasinghe, Jeeva et al. (2016) Imaging Candida Infections in the Host. Methods Mol Biol 1356:69-78
Navarathna, Dhammika H M L P; Munasinghe, Jeeva; Lizak, Martin J et al. (2013) MRI confirms loss of blood-brain barrier integrity in a mouse model of disseminated candidiasis. NMR Biomed 26:1125-34
Pendrak, Michael L; Roberts, David D (2007) Hemoglobin is an effective inducer of hyphal differentiation in Candida albicans. Med Mycol 45:61-71
Pendrak, Michael L; Rodrigues, Rui G; Roberts, David D (2007) Induction of a high affinity fibronectin receptor in Candida albicans by caspofungin: requirements for beta (1,6) glucans and the developmental regulator Hbr1p. Med Mycol 45:157-68
Pendrak, Michael L; Yan, S Steve; Roberts, David D (2004) Sensing the host environment: recognition of hemoglobin by the pathogenic yeast Candida albicans. Arch Biochem Biophys 426:148-56
Pendrak, Michael L; Yan, S Steve; Roberts, David D (2004) Hemoglobin regulates expression of an activator of mating-type locus alpha genes in Candida albicans. Eukaryot Cell 3:764-75
Pendrak, Michael L; Chao, Mark P; Yan, S Steve et al. (2004) Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin. J Biol Chem 279:3426-33
Pendrak, M L; Krutzsch, H C; Roberts, D D (2000) Structural requirements for hemoglobin to induce fibronectin receptor expression in Candida albicans. Biochemistry 39:16110-8
Lyman, C A; Navarro, E; Garrett, K F et al. (1999) Adherence of Candida albicans to bladder mucosa: development and application of a tissue explant assay. Mycoses 42:255-9