Abstract
For host colonization, the human fungal pathogen Candida glabrata is known to utilize a large family of highly related surface-exposed cell wall proteins, the lectin-like epithelial adhesins (Epas). To reveal the structure-function relationships within the entire Epa family, we have performed a large scale functional analysis of the adhesion (A) domains of 17 Epa paralogs in combination with three-dimensional structural studies of selected members with cognate ligands. Our study shows that most EpaA domains exert lectin-like functions and together recognize a wide variety of glycans with terminal galactosides for conferring epithelial cell adhesion. We further identify several conserved and variable structural features within the diverse Epa ligand binding pockets, which affect affinity and specificity. These features rationalize why mere phylogenetic relationships within the Epa family are weak indicators for functional classification and explain how Epa-like adhesins have evolved in C. glabrata and related fungal species.
Highlights
The pathogenic yeast Candida glabrata harbors more than 20 epithelial adhesins (Epas)
The human fungal pathogen Candida glabrata is known to utilize a large family of highly related surface-exposed cell wall proteins, the lectin-like epithelial adhesins (Epas)
Our study shows that most EpaA domains exert lectin-like functions and together recognize a wide variety of glycans with terminal galactosides for conferring epithelial cell adhesion
Summary
The pathogenic yeast Candida glabrata harbors more than 20 epithelial adhesins (Epas). The human fungal pathogen Candida glabrata is known to utilize a large family of highly related surface-exposed cell wall proteins, the lectin-like epithelial adhesins (Epas). Chip-based glycan array screening in combination with Saccharomyces cerevisiae cells presenting EpaA domains or with proteins purified from Escherichia coli has revealed that Epa, Epa, and Epa act as lectins with related ligand binding specificities [12, 14]. To determine the diversity of ligand-binding patterns within the Epa family, we here performed a comprehensive functional characterization of the adhesion domains of 17 Epa family members present in the C. glabrata strain CBS138 using large scale glycan array profiling and proteins purified from E. coli. Our study shows that the Epa adhesin family recognizes a wide variety of ␣- and -linked galactosides as well as nongalactosidic terminal glycans and provides novel insights into the structural motifs that enable ligand discrimination
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