β-1,2- and α-1,2-LinkedOligomannosides Mediate Adherence of Candida albicans Blastospores to Human Enterocytes InVitro

Abstract

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 ␣-1,2-and ␤-1,2-linked mannose residues. ␤-1,2-linked mannosides are also associated with a glycolipid, phospholipomannan, at the C. albicans surface. In order to determine the roles of ␤-1,2 and ␣-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 ␣-1,2 and ␤-1,2 mannan epitopes resulted in a dose-dependent decrease in adhesion (50% of the control with a 60-g/ml MAb concentration). In competitive assays ␤-1,2 and ␣-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 ␣-1,2 and ␤-1,2 oligomannosides showed that these epitopes were shed from the yeast to the enterocyte surface. Taken together, our data indicate that ␣-1,2 and ␤-1,2 oligomannosides are involved in the C. albicans-enterocyte interaction and participate in the adhesion of the yeasts to the mucosal surface.

Genome sequence of the recombinant protein production host Pichia pastoris

“…Indeed, we did not find an ortholog of the S. cerevisiae gene MNN1 (encoding the alpha-1,3-mannosyltransferase) in the Pichia genome. However, Pichia glycoproteins can in some cases be modified with b-1,2-mannose residues 30 , reminiscent of antigenic epitopes on the Candida albicans cell wall 31 . We find the patented P. pastoris AMR2 b-mannosyltransferase in the genome, and three homologs, thus providing the basis for reducing the levels of this undesired glycan modification.…”

Inactivation of CaMIT1 Inhibits Candida albicans Phospholipomannan β-Mannosylation, Reduces Virulence, and Alters Cell Wall Protein β-Mannosylation

“…They act as adhesins for human enterocytes (34) and can prevent colonization of the mouse gut by C. albicans (5). They also bind to macrophages (3,35), stimulating these cells to produce mediators or effectors of the immune response (4,36).…”

Structural Changes of Cell Wall Mannans of Candida guilliermondii IFO 10279 Strain Cells Cultured at High Temperature

“…The cells (2ϫ10 7 ) in 100 to 200 ml aliquots were then inoculated into 200 ml each of YSLM, and the main cultivations were separately conducted in YSLM at 27, 33, 34, 35, 37°C, and 33°C and then at 27°C (33-27°C) for 48 h at each temperature with shaking. After harvesting the cells by centrifugation, the pHs of the supernatants were measured, and the precipitated cells were washed three times with saline by centrifugation.…”

“…[4][5][6][7][8] It is known that the expression of cell surface antigens of C. albicans changes depending on the growth conditions, growth state, and morphology of the cells. 9,10) However, little is known about the entity of the antigenic changes.…”