MOLEKULARE MECHANISMEN DER ADHARENZ VON CANDIDA ALBICANS AN HUMANE KERATINOZYTEN IN VITRO

For a variety of reasons the number of immunosuppressed patients has been increasing in recent years. This increase has led to a concomitant rise in the number of infections of the skin, mucous membranes, digestive tract, and visceral organs caused by the pathogenic yeast Candida albicans. Among other virulence factors, adherence of Candida albicans to human host cells is considered a crucial step in the etiopathogenesis of candidoses. Adherence of the organism to host cells is a requirement for subsequent cell penetration and tissue invasion. In order to understand the pathogenic potential of this yeast, a knowledge of the molecular mechanisms leading to interaction of Candida albicans adhesins with their respective host cell receptors is necessary. Several putative Candida albicans adhesins and counterreceptors have been identified in different cell systems. Some are complex carbohydrates acting as ligands for lectin receptors; others exhibit their adhesive capacities through protein-protein interactions. Many of the mechanisms detected with other cell systems also relate to Candida adherence to human keratinocytes. To delineate the precise molecular mechanisms involved, an in vitro model probing the adherence of Candida albicans to cultured human keratinocytes was established. Adherence was found to be mediated by multiple mechanisms such as lectin-carbohydrate and protein-protein interactions, various other factors, and the secretion of Candida albicans acid protease. Thus, a hypothetical multi-step model for the adherence of Candida albicans to human keratinocytes is proposed. In such a model, the high-affinity binding of the organism to host cells necessary for tissue invasion is preceded by dynamic changes of the Candida cell surface and several initiating low-affinity interactions with the target keratinocyte.