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

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Abstract
The pathogenic yeast Candida albicans 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 C. albicans was assessed in a mouse model. A selected virulent strain of C. albicans (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 C. albicans -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.