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.
Highlights
The fungus, Candida albicans is a significant human pathogen
The fungus Candida albicans can proliferate in the mouth, causing oropharyngeal candidiasis
One mechanism by which C. albicans invades both the epithelial cell lining of the oropharynx and the endothelial cell lining of the blood vessels is by inducing its own uptake
Summary
The fungus, Candida albicans is a significant human pathogen. In hospitalized patients, this organism disseminates hematogenously and infects virtually all organs. To persist within the human host and cause disease, C. albicans must be able to adhere to and invade host cells or tissues while resisting the stress caused by host-derived reactive oxygen intermediates and antimicrobial peptides [2,3,4,5]. Heat shock proteins play an important role in each of these activities. In some bacteria and parasites, members of the Hsp and Hsp100 family of heat shock proteins are required for resistance to host-induced stress [10,11,12]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.