Beta-1,2- and alpha-1,2-linked oligomannosides mediate adherence of Candida albicans blastospores to human enterocytes in vitro.
Candida albicans is a commensal dimorphic yeast of the digestive tract that causes hematogenously disseminated infections in immunocompromised individuals. Endogenous invasive candidiasis develops from C. albicans adhering to the intestinal epithelium. Adherence is mediated by the cell wall surface, a domain composed essentially of mannopyranosyl residues bound to proteins, the N-linked moiety of which comprises sequences of alpha-1,2- and beta-1,2-linked mannose residues. Beta-1,2-linked mannosides are also associated with a glycolipid, phospholipomannan, at the C. albicans surface. In order to determine the roles of beta-1,2 and alpha-1,2 oligomannosides in the C. albicans-enterocyte interaction, we developed a model of adhesion of C. albicans VW32 blastospores to the apical regions of differentiated Caco-2 cells. Preincubation of yeasts with monoclonal antibodies (MAbs) specific for alpha-1,2 and beta-1,2 mannan epitopes resulted in a dose-dependent decrease in adhesion (50% of the control with a 60- micro g/ml MAb concentration). In competitive assays beta-1,2 and alpha-1,2 tetramannosides were the most potent carbohydrate inhibitors, with 50% inhibitory concentrations of 2.58 and 6.99 mM, respectively. Immunolocalization on infected monolayers with MAbs specific for alpha-1,2 and beta-1,2 oligomannosides showed that these epitopes were shed from the yeast to the enterocyte surface. Taken together, our data indicate that alpha-1,2 and beta-1,2 oligomannosides are involved in the C. albicans-enterocyte interaction and participate in the adhesion of the yeasts to the mucosal surface.
Dalle
Fredéric
F
Laboratoire de Parasitologie Mycologie, Hôpital du Bocage, Dijon, France.
Jouault
Thierry
T
Trinel
Pierre André
PA
Esnault
Jacques
J
Mallet
Jean Maurice
JM
d'Athis
Philippe
P
Poulain
Daniel
D
Bonnin
Alain
A
D018938:Caco-2 Cells; D002176:Candida albicans / Q000472:pathogenicity* / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D020895:Enterocytes / Q000382:microbiology*; D006801:Humans; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology
D009844:Oligosaccharides; D011134:Polysaccharides; C028569:oligomannoside