Host Cell Invasion and Virulence Mediated by Candida albicans Ssa1

PLoS Pathogens

Mira Edgerton¹  Jashanjot S. Bajwa¹  Jianing N. Sun¹  Angela Thompson²  Anna Dongari-Bagtzoglou²  Helena Kashleva²  Scott G. Filler³  Yaoping Liu³  Norma V. Solis³  Quynh T. Phan³ 

[1] Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, New York, United States of America;Division of Periodontology, School of Dental Medicine, University of Connecticut, Farmington, Connecticut, United States of America;Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America

关键词: C;    ida albicans;    Epithelial cells;    Host cells;    Mouse models;    Endothelial cells;    Endocytosis;    C;    idiasis;    Yeast infections;   

DOI  :  10.1371/journal.ppat.1001181

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY