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Antimicrobial Agents and Chemotherapy, December 2002, p. 3869-3876, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3869-3876.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Françoise Dromer,1 Reynald Chevalier,2 Boualem Sendid,3 Luce Improvisi,1 Thierry Jouault,3 Raymond Robert,4 Jean Maurice Mallet,2 and Daniel Poulain3*

Unité de Mycologie Moléculaire, Institut Pasteur, 75015 Paris,1 Département de Chimie, Ecole Normale Supérieure, 75005 Paris,2 Equipe Inserm 9915, Faculté de Médecine, Pôle Recherche, Centre Hospitalier-Universitaire, 59045 Lille,3 Laboratoire de Parasitologie, Faculté de Pharmacie, Boulevard Daviers, 49000 Angers, France4

Received 1 April 2002/ Returned for modification 13 May 2002/ Accepted 15 July 2002

The pathogenic yeast Candida albicans displays at its cell surface ß-1,2 oligomannosides (ß-1,2-Mans). In contrast to the ubiquitous {alpha}-Mans, ß-1,2-Mans bind to galectin-3, a major endogenous lectin expressed on epithelial cells. The specific role of ß-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 ß-1,2-Man epitopes) induced more intense and sustained colonization than an avirulent strain (expressing less ß-1,2-Man epitopes). Synthetic ({Sigma}) ß-and {alpha}-linked tetramannosides with antigenicities that mimicked the antigenicities of C. albicans-derived oligomannosides were then constructed. Oral administration of {Sigma}ß-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 {Sigma}{alpha}-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.


* Corresponding author. Mailing address: Inserm E9915, Faculté de Médecine, Pôle Recherche, CHRU, Place de Verdun, 59045 Lille Cedex, France. Phone: 33 3 20 62 34 20. Fax: 33 3 20 62 34 16. E-mail: dpoulain{at}univ-lille2.fr.


Antimicrobial Agents and Chemotherapy, December 2002, p. 3869-3876, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3869-3876.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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