title: Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice.
abstract: Oroesophageal candidiasis is caused by the combined action of fungal virulence factors and host inflammatory responses when protective immunity is absent. Hyphal wall protein 1 (Hwp1) on germ tubes and true hyphae of Candida albicans forms covalent cross-links to buccal epithelial cells in vitro by functioning as a substrate for mammalian transglutaminases. In this study, beige-athymic (bg/bg-nu/nu) or transgenic epsilon 26 mice that have combined natural killer and T cell defects did not succumb to candidiasis after oral administration of C. albicans strains with inactivated HWP1 genes, whereas mice given isogenic strains of C. albicans that had a single copy of HWP1 survived only 2-3 weeks. Illness correlated with extensive alterations of the lingual and esophageal mucosa that were absent in mice given the hwp1/hwp1 mutant. HWP1 is a promising target for development of antifungal drugs for treatment of oroesophageal candidiasis.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210-1239, USA. sundstrom.1@osu.edu
authors.forename: Paula
authors.initials: P
authors.lastname: Sundstrom
authors.forename: Edward
authors.initials: E
authors.lastname: Balish
authors.forename: Carl M
authors.initials: CM
authors.lastname: Allen
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity; D002177:Candidiasis / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D002180:Candidiasis, Oral / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D004064:Digestive System / Q000382:microbiology; D004935:Esophageal Diseases / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D004947:Esophagus / Q000382:microbiology / Q000473:pathology; D005260:Female; D005656:Fungal Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D015996:Survival Rate; D014059:Tongue / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; D008562:Membrane Glycoproteins