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Paula Sundstrom, Edward Balish, Carl M. Allen, Essential Role of the Candida albicans Transglutaminase Substrate, Hyphal Wall Protein 1, in Lethal Oroesophageal Candidiasis in Immunodeficient Mice, The Journal of Infectious Diseases, Volume 185, Issue 4, 15 February 2002, Pages 521–530, https://doi.org/10.1086/338836
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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 formammalian transglutaminases. In this study, beigeathymic (bg/bg-nu/nu) or transgenic ∈ 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.