Host Cell Invasion and Virulence Mediated by Candida albicans Ssa1

University of Massachusetts Medical School, United States of America
PLoS Pathogens (Impact Factor: 7.56). 11/2010; 6(11):e1001181. DOI: 10.1371/journal.ppat.1001181
Source: PubMed


Candida albicans Ssa1 and Ssa2 are members of the HSP70 family of heat shock proteins that are expressed on the cell surface and function as receptors for antimicrobial peptides such as histatins. We investigated the role of Ssa1 and Ssa2 in mediating pathogenic host cell interactions and virulence. A C. albicans ssa1Δ/Δ mutant had attenuated virulence in murine models of disseminated and oropharyngeal candidiasis, whereas an ssa2Δ/Δ mutant did not. In vitro studies revealed that the ssa1Δ/Δ mutant caused markedly less damage to endothelial cells and oral epithelial cell lines. Also, the ssa1Δ/Δ mutant had defective binding to endothelial cell N-cadherin and epithelial cell E-cadherin, receptors that mediate host cell endocytosis of C. albicans. As a result, this mutant had impaired capacity to induce its own endocytosis by endothelial cells and oral epithelial cells. Latex beads coated with recombinant Ssa1 were avidly endocytosed by both endothelial cells and oral epithelial cells, demonstrating that Ssa1 is sufficient to induce host cell endocytosis. These results indicate that Ssa1 is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and is critical for C. albicans to cause maximal damage to host cells and induce disseminated and oropharyngeal disease.

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    • "The observation that invasion-defective C. albicans mutants display attenuated virulence in murine models of OPC and HDC is evidence of the critical importance of invasion to virulence (Phan et al. 2000; Sanchez et al. 2004; Park et al. 2005; Chiang et al. 2007). Invasion into both cell types occurs in part by endocytosis, which is induced when the C. albicans invasins Als3p and Ssa1p interact with receptors expressed on the surface of endothelial and epithelial cells (Phan et al. 2007; Sun et al. 2010). These receptors include N-and E-cadherin, HSP90B1, the epidermal growth factor receptor (EGFR), and ERBB2 (also known as HER2) (Phan et al. 2005, 2007; Liu et al. 2011; Zhu et al. 2012). "
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