Adhesion of Candida albicans to host tissues is important in the hematogenous spread of the organism. Adherence to the vascular lining determines homing specificity resulting in targeting of specific organs and tissues. Analysis of leukocyte/endothelial-cell adhesion has demonstrated that the shear forces associated with blood flow dictate the type of adhesion receptor/ligand interactions that regulates the binding event. Adhesion of C. albicans to host tissue ligands have not been previously examined under shear; thus, it is not clear if any of the known C. albicans adhesins can function in blood flow. The objective of this project is to use novel, in vitro, flow adhesion assays and intravital microscopy to identify C. albicans shear-dependent adhesive interactions with host ligands. The following Specific Aims will be pursued. 1) Interactions between C. albicans and endothelial cells, platelets, marginating leukocytes, and extracellular matrix components will be examined under shear forces that approximate blood flow. 2) The role of known adhesins (C. albicans and host) in the interactions defined in Specific Aim 1 will be determined. 3) Identification and characterization of novel, shear-dependent adhesins will be sought. 4) Using intravital microscopy, interactions between C. albicans and vessels in exteriorized mouse mesentery will be done directly in the animal to confirm the importance of any interaction defined in the in vitro assays.
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