Global cell surface conformational shift mediated by a Candida albicans adhesin.
Candida albicans maintains both commensal and pathogenic states in humans. Both states are dependent on cell surface-expressed adhesins, including those of the Als family. Heterologous expression of Als5p at the surface of Saccharomyces cerevisiae results in Als5p-mediated adhesion to various ligands, followed by formation of multicellular aggregates. Following adhesion of one region of the cell to fibronectin-coated beads, the entire surface of the cells became competent to mediate cell-cell aggregation. Aggregates formed in the presence of metabolic inhibitors or signal transduction inhibitors but were reduced in the presence of 8-anilino-1-naphthalene-sulfonic acid (ANS) or Congo Red (CR), perturbants that inhibit protein structural transitions. These perturbants also inhibited aggregation of C. albicans. An increase in ANS fluorescence, which accompanied Als-dependent cellular adhesion, indicated an increase in cell surface hydrophobicity. In addition, C. albicans and Als5p-expressing S. cerevisiae showed an aggregation-induced birefringence indicative of order on the cell surface. The increase in birefringence did not occur in the presence of the aggregation disruptants ANS and CR. These results suggest a model for Als5p-mediated aggregation in which an adhesion-triggered change in the conformation of Als5p propagates around the cell surface, forming ordered aggregation-competent regions.
Department of Biology, Hunter College, 695 Park Ave., New York, NY 10021, USA.
Jason M
JM
Rauceo
Nand K
NK
Gaur
Kyeng-Gea
KG
Lee
John E
JE
Edwards
Stephen A
SA
Klotz
Peter N
PN
Lipke
D000817:Anilino Naphthalenesulfonates / Q000494:pharmacology; D001718:Birefringence; D002176:Candida albicans / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D003224:Congo Red / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D014170:Transformation, Genetic
C109455:ALA1 protein, Candida albicans; D000817:Anilino Naphthalenesulfonates; D015815:Cell Adhesion Molecules; D005656:Fungal Proteins; D008024:Ligands; D003224:Congo Red; C027132:1-anilino-8-naphthalenesulfonate