Molecular mimicry in Candida albicans. Role of an integrin analogue in adhesion of the yeast to human endothelium.

Abstract

Hematogenous infection with the yeast Candida albicans now occurs with increasing frequency in the neonate, the immunocompromised patient, and the hyperglycemic or hyperalimented host. Yeast-phase C. albicans expresses a protein that is antigenically and structurally related to CD11b/CD18, a member of the 2 integrins and a well-characterized adhesin for mammalian neutrophils. Both the neutrophil protein and its analogue in C. albicans have an identical affinity for the C3 ligand iC3b, and both proteins are significantly increased in expression at 370C. Given these several similarities, we therefore studied the role of the integrin analogue on C. albicans in the adhesion of the yeast to human umbilical vein endothelium (HUVE).After growth of C. albicans in 20 mM D-glucose, as opposed to 20 mM L-glutamate, flow cytometric analysis with monoclonal antibodies recognizing the a-subunit of CDMMb/ CD18 demonstrated a 25.0% increase in mean channel fluorescence (range 18.4-31.8%), as well as an increased percentage of yeasts fluorescing (P < 0.02). This increased intensity of fluorescence, which corresponds to increased expression of the integrin analogue, also correlated with a significant increase of 30-80% in adhesion of glucose-grown C. albicans to HUVE (P < 0.02). Blockade of the integrin analogue on C. albicans by monoclonal antibodies recognizing adhesive epitopes on neutrophil CD11b/CD18 inhibited glucose-enhanced adhesion of C. albicans to HUVE. Incubation of glucose-grown C. albicans with saturating concentrations of purified human iC3b, the ligand for CD1lb/CD18, reduced adhesion of the yeast to HUVE by 49.7%, whereas BSA in equimolar concentration had no effect (P < 0.001). These results identify a glucose-responsive integrin analogue on C. albicans as one of possibly several cellular structures that mediate adhesion of the yeast to human endothelium. (J. Clin. Invest. 1991. 87:1896-1902

Oral Colonization By Candida Albicans

“…The iC3b binding protein(s) discussed below contributed to adherence to umbilical vein endothelium. Two monoclonal antibodies that recognize human integrin subunit tm partially inhibited adherence (Gustafson et al, 1991).…”

“…(3) In vitro growth conditions of the fungus-such as temperature (Lee and King, 1983), medium composition (Alloush et al, 1996;Yan et al, 1998b), carbon source (McCourtie and Douglas, 1985;Gustafson et al, 1991), or the presence of a specific inducer (Yan et al, 1998a)-may alter the expression of an adhesin.…”

“…Both BECs and VECs stained with antifibronectin antibody, and yeast cells pre-treated with fibronectin showed reduced binding to BECs and VECs compared with untreated cells (Skerl et al, 1984;Kalo et al, 1988). The complement fragment iG3b has also been implicated as a ligand involved in epithelial and endothelial cell adherence (Gustafson et al, 1991;Bendel and Hostetter, 1993;Bendel et al, 1995; also see reviews by Hostetter, 1994;Chaffin et al, 1998). Glucose-grown cells express more iC3b receptor than glutamate-grown cells and show increased binding to human umbilical vein cells (HUVCs) (Gustafson et al, 1991).…”

“…The complement fragment iG3b has also been implicated as a ligand involved in epithelial and endothelial cell adherence (Gustafson et al, 1991;Bendel and Hostetter, 1993;Bendel et al, 1995; also see reviews by Hostetter, 1994;Chaffin et al, 1998). Glucose-grown cells express more iC3b receptor than glutamate-grown cells and show increased binding to human umbilical vein cells (HUVCs) (Gustafson et al, 1991). Antibody to the human iC3b integrin receptor, iC3b, and several RGD (arginine-glycine-aspartic acid)-containing peptides from iC3b reduced binding of C. albicans to HUVCs or HeLa cells (Bendel and Hostetter, 1993).…”

The highly immunogenic enolase and Hsp70p are adventitious Candida albicans cell wall proteins

“…Among these proteins, receptors for complement factors (Calderone et al, 1988;Gustafson et al, 1991;Alaei et al, 1993), as well as for fibrinogen (Bouali et al, 1987;Martinez et al, 1994), fibronectin (Kalon et al, 1988;Klotz & Smith, 1991 ;Klotz et al, 1994), laminin (Bouchara et al, 1990;Lopez-Ribot et al, 1994) and other extracellular matrix genes encoding these proteins, the presence of these proteins on the cell surface was investigated and it was concluded that these and probably other cytosolic proteins can be bound to cell walls in vitro, as can happen in vivo. Their presence in the C. albicans cell wall seems to be a consequence of cell lysis and not a result of a secretory process.…”