Synthetic analogues of beta-1,2 oligomannosides prevent intestinal colonization by the pathogenic yeast Candida albicans.
The pathogenic yeast Candida albicans displays at its cell surface beta-1,2 oligomannosides (beta-1,2-Mans). In contrast to the ubiquitous alpha-Mans, beta-1,2-Mans bind to galectin-3, a major endogenous lectin expressed on epithelial cells. The specific role of beta-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 beta-1,2-Man epitopes) induced more intense and sustained colonization than an avirulent strain (expressing less beta-1,2-Man epitopes). Synthetic (Sigma) beta-and alpha-linked tetramannosides with antigenicities that mimicked the antigenicities of C. albicans-derived oligomannosides were then constructed. Oral administration of Sigmabeta-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 Sigmaalpha-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.
Dromer
Françoise
F
Unité de Mycologie Moléculaire, Institut Pasteur, 75015 Paris, France.
Chevalier
Reynald
R
Sendid
Boualem
B
Improvisi
Luce
L
Jouault
Thierry
T
Robert
Raymond
R
Mallet
Jean Maurice
JM
Poulain
Daniel
D
D000818:Animals; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D002177:Candidiasis / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D051379:Mice; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
D009844:Oligosaccharides; C028569:oligomannoside