Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice

J Infect Dis. 2002 Feb 15;185(4):521-30. doi: 10.1086/338836. Epub 2002 Jan 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Candida albicans / pathogenicity
  • Candidiasis / etiology*
  • Candidiasis / immunology
  • Candidiasis / mortality
  • Candidiasis, Oral / etiology*
  • Candidiasis, Oral / immunology
  • Candidiasis, Oral / mortality
  • Digestive System / microbiology
  • Esophageal Diseases / etiology*
  • Esophageal Diseases / immunology
  • Esophageal Diseases / mortality
  • Esophagus / microbiology
  • Esophagus / pathology
  • Female
  • Fungal Proteins*
  • Humans
  • Male
  • Membrane Glycoproteins / physiology*
  • Mice
  • Survival Rate
  • Tongue / microbiology
  • Tongue / pathology
  • Virulence

Substances

  • Fungal Proteins
  • HWP1 protein, Candida albicans
  • Membrane Glycoproteins