Synthetic Analogues of β-1,2 Oligomannosides Prevent Intestinal Colonization by the Pathogenic Yeast <i>Candida albicans</i>

DOI Web Site 被引用文献2件
  • Françoise Dromer
    Unité de Mycologie Moléculaire, Institut Pasteur, 75015 Paris
  • Reynald Chevalier
    Département de Chimie, Ecole Normale Supérieure, 75005 Paris
  • Boualem Sendid
    Equipe Inserm 9915, Faculté de Médecine, Pôle Recherche, Centre Hospitalier-Universitaire, 59045 Lille
  • Luce Improvisi
    Unité de Mycologie Moléculaire, Institut Pasteur, 75015 Paris
  • Thierry Jouault
    Equipe Inserm 9915, Faculté de Médecine, Pôle Recherche, Centre Hospitalier-Universitaire, 59045 Lille
  • Raymond Robert
    Laboratoire de Parasitologie, Faculté de Pharmacie, Boulevard Daviers, 49000 Angers, France
  • Jean Maurice Mallet
    Département de Chimie, Ecole Normale Supérieure, 75005 Paris
  • Daniel Poulain
    Equipe Inserm 9915, Faculté de Médecine, Pôle Recherche, Centre Hospitalier-Universitaire, 59045 Lille

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<jats:title>ABSTRACT</jats:title> <jats:p> The pathogenic yeast <jats:italic>Candida albicans</jats:italic> displays at its cell surface β-1,2 oligomannosides (β-1,2-Mans). In contrast to the ubiquitous α-Mans, β-1,2-Mans bind to galectin-3, a major endogenous lectin expressed on epithelial cells. The specific role of β-1,2-Mans in colonization of the gut by <jats:italic>C. albicans</jats:italic> was assessed in a mouse model. A selected virulent strain of <jats:italic>C. albicans</jats:italic> (expressing more β-1,2-Man epitopes) induced more intense and sustained colonization than an avirulent strain (expressing less β-1,2-Man epitopes). Synthetic (Σ) β-and α-linked tetramannosides with antigenicities that mimicked the antigenicities of <jats:italic>C. albicans</jats:italic> -derived oligomannosides were then constructed. Oral administration of Σβ-1,2-Man (30 mg/kg of body weight) prior to inoculation with the virulent strain resulted in almost complete eradication of yeasts from stool samples, whereas administration of Σα-Man at the same dose did not. As most cases of human systemic candidiasis are endogenous in origin, this first demonstration that a synthetic analogue of a yeast adhesin can prevent yeast colonization in the gut opens the possibility of new prophylactic strategies. </jats:p>

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