Mechanisms of adherence of Candida albicans to cultured human epidermal keratinocytes.

AUTOR(ES)

Ollert, M W

RESUMO

We established an in vitro adherence model with primarily cultured human keratinocytes as target cells which allows for the investigation of the molecular mechanisms that are responsible for Candida albicans host cell attachment in the initiation of cutaneous candidosis. The extent of C. albicans binding to cultured human keratinocytes was dependent on the yeast inoculum size and the incubation temperature. Heat and paraform-aldehyde treatment of yeasts completely abolished the binding activity of C. albicans. Of the different Candida species tested, C. albicans was by far the most adhesive species. C. albicans adherence was blocked by the acid protease inhibitor pepstatin A and the metabolic inhibitor sodium azide. The latter, however, was much less effective when yeasts were preincubated, suggesting that sodium azide was mainly acting on the keratinocytes. The extracellular matrix protein fibronectin was slightly inhibitory, whereas the fibronectin-derived peptides RGD and RGDS were not able to prevent attachment. PepTite-2000, another RGD-containing synthetic peptide, reduced C. albicans adherence by a margin of 25% (P < 0.005). CDPGYIGSR-NH2, which is a synthetic adhesive peptide derived from the laminin B chain, was much more efficient in its inhibitory activity than the RGD peptides and reduced C. albicans adherence to cultured human keratinocytes up to 76% (P < 0.001). Laminin itself and the synthetic pentapeptide YIGSR were less active. A dose-dependent reduction in adherence was also observed with collagen type III. Additionally, saccharides were tested for their potential to inhibit C. albicans attachment to keratinocytes. The most potent competitive saccharide inhibitors of C. albicans adherence to human keratinocytes were the amino sugars D-(+)-glucosamine and D-(+)-galactosamine with one isolate of C. albicans (4918) and D-(+)-glucosamine and alpha-D-(+)-fucose with another C. albicans isolate (Sp-1). Collectively, our data suggest the existence of multiple molecular mechanisms such as protein-protein, lectin-carbohydrate, and yeast-yeast coaggregational interactions that are responsible for optimal C. albicans attachment to cultured human keratinocytes.

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