Inhibition of hydrophobic protein-mediated Candida albicans attachment to endothelial cells during physiologic shear flow

Adhesion interactions during hematogenous dissemination of Candida albicans likely involve a complex array of host and fungal factors, Possible C, alb icans factors include changes in cell surface hydrophobicity and exposed an tigens that have been shown in static adhesion assays to influence attachme nt events. T Ve used a novel in vitro shear analysis system to investigate host-pathogen interactions and the role of fungal cell surface hydrophobici ty in adhesion events with human endothelial cells under simulated physiolo gic shear. Endothelial monolayers were grown capillary tubes and tested wit h and without interleukin-1 beta activation in buffered medium containing h uman serum. I Hydrophobic and hydrophilic stationary-phase C, albicans yeas t cells were infused into the system under shear flow and found to adhere w ith widely varying efficiencies, The average number of adherent foci was de termined from multiple fields, sampled cia video microscopy, between 8 and 12 min after infusion. Hydrophobic C, albicans cells demonstrated significa ntly more heterotypic binding events (Candida-endothelial cell) and greater homotypic binding events (Candida-Candida) than hydrophilic yeast cells, C ytokine activation of the endothelium significantly increased binding by hy drophobic C. albicans compared to unactivated host cells. Preincubation of hydrophobic yeast cells with a monoclonal antibody against hydrophobic cell wall proteins significantly blocked adhesion interactions with the endothe lial mono-layers, Because the antibody also blocks C. albicans binding to l aminin and fibronectin, results suggest that vascular adhesion events with endothelial cells and exposed extracellular matrix may be blocked during C, albicans dissemination. Future studies will address the protective efficac y of blocking or redirecting bloodborne fungal cells to favor host defense mechanisms.