title: Mechanisms of Candida albicans trafficking to the brain.
abstract: During hematogenously disseminated disease, Candida albicans infects most organs, including the brain. We discovered that a C. albicans vps51Δ/Δ mutant had significantly increased tropism for the brain in the mouse model of disseminated disease. To investigate the mechanisms of this enhanced trafficking to the brain, we studied the interactions of wild-type C. albicans and the vps51Δ/Δ mutant with brain microvascular endothelial cells in vitro. These studies revealed that C. albicans invasion of brain endothelial cells is mediated by the fungal invasins, Als3 and Ssa1. Als3 binds to the gp96 heat shock protein, which is expressed on the surface of brain endothelial cells, but not human umbilical vein endothelial cells, whereas Ssa1 binds to a brain endothelial cell receptor other than gp96. The vps51Δ/Δ mutant has increased surface expression of Als3, which is a major cause of the increased capacity of this mutant to both invade brain endothelial cells in vitro and traffic to the brain in mice. Therefore, during disseminated disease, C. albicans traffics to and infects the brain by binding to gp96, a unique receptor that is expressed specifically on the surface of brain endothelial cells.
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
authors: Yaoping
authors: Y
authors: Liu
authors: Rahul
authors: R
authors: Mittal
authors: Norma V
authors: NV
authors: Solis
authors: Nemani V
authors: NV
authors: Prasadarao
authors: Scott G
authors: SG
authors: Filler
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000382:microbiology*; D002176:Candida albicans / Q000378:metabolism* / Q000472:pathogenicity*; D002352:Carrier Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000382:microbiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D021381:Protein Transport
chemical_list: C113620:ALS3 protein, Candida albicans; D002352:Carrier Proteins; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin