title: Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro.
abstract: Rhizopus oryzae is the most common cause of zygomycosis, a life-threatening infection that usually occurs in immunocompromised patients. A characteristic hallmark of zygomycosis is angioinvasion by the fungus, resulting in thrombosis and subsequent tissue necrosis. Interactions between R. oryzae and vascular endothelial cells are therefore likely of central importance to the organism's pathogenetic strategy. We studied the ability of R. oryzae to adhere to and damage human umbilical vein endothelial cells (HUVECs) in vitro. We report that R. oryzae spores and germ tubes adhere to HUVECs, whereas only spores adhere to subendothelial matrix proteins. Additionally, R. oryzae damages endothelial cells. This endothelial cell damage requires direct contact and subsequent phagocytosis of the fungus. Surprisingly, R. oryzae viability was not required for damage, but phagocytosis was required for dead R. oryzae to cause damage. These results elucidate the nature of R. oryzae-endothelial cell interactions, which are likely central to the angioinvasion and tissue necrosis seen during zygomycotic infections. The fact that dead R. oryzae damage human endothelial cells may, in part, explain the lack of efficacy of fungicidal agents during clinical disease.
authors.affiliation: Division of Infectious Diseases, St. John's Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Bldg. RB2, 1124 West Carson Street, Torrance, CA 90502, USA. ibrahim@labiomed.org
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Valentina
authors.initials: V
authors.lastname: Avanessian
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D015638:Cytochalasin D / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D009091:Mucormycosis / Q000276:immunology* / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology*; D012233:Rhizopus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D