Adherence of Candida to Cultured Vascular Endothelial Cells: Mechanisms of Attachment and Endothelial Cell Penetration

Abstract

To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells. We enhanced or inhibited adherence in order to probe mechanisms of attachment. Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10(2)-10(5) cfu, r = .99, P less than .01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P less than .01). Candida immune serum blocked attachment (greater than 95% inhibition; P less than .001), however, this activity was abolished by immunoprecipitation of immune serum with C. albicans mannan (P less than .001) and was unaffected by immunoprecipitation with S. cerevisiae mannan or by adsorption with particulate chitin. Adherence was diminished by exposing C. albicans to heat (greater than 99% inhibition; P less than .01), UV light (98% inhibition; P less than .01), or sodium periodate (greater than 72% inhibition; P less than .01). An extract from heat-exposed C. albicans blocked adherence (greater than 51% inhibition; P less than .001). Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes. Cytochalasin B blocked incorporation without blocking surface attachment.

A Role of Secreted Proteinase of Candida albicans for the Invasion of Chick Chorio‐Allantoic Membrane

“…On the contrary, there are many reports claiming that host cellular structures show scarcely any changes in the vicinity of Candida cells (1,3,5,7,15,26). Our electron micrographs showed the two aspects of the tissue disintegration: detachment of tissue cells due to the dissolution of desmosomes and the degeneration of host cells due to phagocytosed yeast cells.…”

Distinct mechanisms of epithelial adhesion for Candida albicans and Candida tropicalis. Identification of the participating ligands and development of inhibitory peptides.

“…of 50-60 and 165 kD are less adherent to buccal epithelial cells (42). In comparative studies with human or porcine endothelium, C. albicans and C. tropicalis were generally more adherent than other Candida species or S. cerevisiae (49,50), an indication that adhesion may well correlate strongly with pathogenicity.…”

Experimental Model of Candida Albicans (Serotypes a and B) Adherence in Vitro

“…Fibrils mediating the adherence of C. albicans to surfaces have also been observed (27,31,41) and seem to be analogous to the fimbriae of bacteria (8,36) which play an important role in the establishment of adherence (38). The precise chemical nature of these morphological structures is still unknown (11) but they represent distinct adhering entities with a high ability to adhere to epithelial cells.…”