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Method for Identifying an Agent that Inhibits Candida Albicans-Mediated Host Cell Differentiation

The stratified squamous epithelium of wet mucosal surfaces of immunocompromised mammalian hosts may become heavily invaded by the opportunistic fungal pathogen, Candida albicans. A hallmark of pseudomembranous candidiasis or thrush is the presence of hyperkeratinization, which provides an environment that supports heavy growth of C. albicans.

Dartmouth researchers have now found that C. albicans affects the expression of molecular markers of differentiation. Specifically, it has been demonstrated that C. albicans induces behavior similar to the movement-based mechanism leading to cell–cell adhesions of epidermal keratinocytes. The keratinocyte response also includes the expression of the late differentiation markers keratin 13 and SPRR3 and loss of calprotectin. The keratinocyte response is not simply a general response to the presence of a foreign organism, as it does not occur in the presence of the non-pathogenic yeast Saccharomyces cerevisiae. These studies show the potential for C. albicans to manipulate oral stratified epithelial cells to a state of differentiation that is favorable for its growth and survival. Therefore, inhibition of keratinocyte differentiation or the production and/or secretion of C. albicans factors that induce keratinocyte differentiation is an approach useful in the prevention or treatment of candidiaisis. The initial findings have been published in the journal Cellular Microbiology (Rollenhagen et al. 11:946 (2009)).

This technology is claimed in the published PCT Application No. PCT/US2010/045476. We are seeking an industrial partner interested in its commercialization. (Ref: J488)

Last Updated: 7/24/12