title: Host cell invasion and virulence mediated by Candida albicans Ssa1.
abstract: 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.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, New York, United States of America.
authors.forename: Jianing N
authors.initials: JN
authors.lastname: Sun
authors.forename: Norma V
authors.initials: NV
authors.lastname: Solis
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Phan
authors.forename: Jashanjot S
authors.initials: JS
authors.lastname: Bajwa
authors.forename: Helena
authors.initials: H
authors.lastname: Kashleva
authors.forename: Angela
authors.initials: A
authors.lastname: Thompson
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Liu
authors.forename: Anna
authors.initials: A
authors.lastname: Dongari-Bagtzoglou
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D004269:DNA, Bacterial / Q000235:genetics; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics*
chemical_list: D015820:Cadherins; D004269:DNA, Bacterial; D018840:HSP70 Heat-Shock Proteins