Molecular basis of fungal adherence to endothelial and epithelial cells.

This chapter focuses on fungal adhesins that have been characterized at the genetic level and that mediate adherence to host constituents. These adhesins include Als proteins, Hwp1p, Eap1p, Csh1p, and other less well characterized proteins. ALS1 is part of a gene family that is characterized by the presence of conserved tandem repeats. The ALS gene family contains at least eight members, ALS1, ALS2, ALS3, ALS4, ALS5, ALS6, ALS7, and ALS9. A comprehensive study of the binding specificity of Als proteins expressed in Saccharomyces cerevisiae found that that Als1p, Als3p, and Als5p mediate adherence to a broad variety of host substrates, including endothelial cells, oral epithelial cells, collagen, fibronectin, and laminin. Fragments of genes with homology to the Candida albicans ALS gene family have been detected in Candida dubliniensis and Candida tropicalis. Several studies have demonstrated that Aspergillus fumigatus conidia and hyphae adhere specifically to a variety of host substrates including laminin, fibrinogen, fibronectin, and pulmonary epithelial cells. The identification and characterization of fungal adhesins have been greatly facilitated by the development of powerful molecular biology tools and the recently completed fungal genome-sequencing projects. Furthermore, many important fungal adhesins will probably be glycosylphosphatidylinositol (GPI)-linked proteins with serine- and threonine-rich tandem repeats in their central domains. Identification of these adhesins is important because it provides insight into the mechanisms of fungal pathogenicity, as well as potential therapeutic targets.