Full text loading...
Chapter 13 : Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells
Category: Fungi and Fungal Pathogenesis
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
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.
Key Concept Ranking
- Tumor Necrosis Factor alpha
Conceptual model of structure-function relationships in Als family proteins. Als proteins are composed of three general components: an N-terminal domain, serine/threonine-rich tandem repeats, and a serine/threonine-rich C-terminal domain containing a GPI anchor that is bound to the C. albicans cell wall. As illustrated, Als proteins contain multiple conserved antiparallel β-sheet regions (CR1–n) that are separated by extended spans, characteristic of the immunoglobulin superfamily. Projecting from the β-sheet domains are loop/coil structures containing the hypervariable regions (HVRs). The three-dimensional physicochemical properties of specific Als protein hypervariable regions probably govern interactions with host substrates that confer adhesive and invasive functions to C. albicans. For illustrative purposes, only three N-terminal β-sheet/coil domains and their respective conserved region and hypervariable region components are shown.