Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 185, Issue 4, Pages 521-530Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/338836
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- NIDCR NIH HHS [DE-11375, DE-13968] Funding Source: Medline
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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.
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