Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, New York, United States of America.
PLoS Pathog. 2010 Nov 11;6(11):e1001181. doi: 10.1371/journal.ppat.1001181.
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.
白色念珠菌 Ssa1 和 Ssa2 是热休克蛋白 HSP70 家族的成员，它们在细胞表面表达，作为抗菌肽（如组织蛋白酶）的受体发挥作用。我们研究了 Ssa1 和 Ssa2 在介导致病性宿主细胞相互作用和毒力中的作用。白色念珠菌 ssa1Δ/Δ 突变体在播散性和口咽念珠菌病的小鼠模型中毒力减弱，而 ssa2Δ/Δ 突变体则没有。体外研究表明，ssa1Δ/Δ 突变体对血管内皮细胞和口腔上皮细胞系造成的损伤明显减少。此外，ssa1Δ/Δ 突变体与内皮细胞 N-钙粘蛋白和上皮细胞 E-钙粘蛋白的结合能力受损，这是介导白色念珠菌宿主细胞内吞作用的受体。因此，该突变体诱导内皮细胞和口腔上皮细胞自身内吞的能力受损。包被重组 Ssa1 的乳胶珠被内皮细胞和口腔上皮细胞强烈内吞，表明 Ssa1 足以诱导宿主细胞内吞。这些结果表明 Ssa1 是一种新型的侵袭素，它与宿主细胞钙粘蛋白结合，诱导宿主细胞内吞，并对白色念珠菌对宿主细胞造成最大损伤和诱导播散性和口咽疾病至关重要。
