Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice.
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.
Sundstrom
Paula
P
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
Balish
Edward
E
Allen
Carl M
CM
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
D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; D008562:Membrane Glycoproteins