Adhesins in Candida glabrata

Abstract

The human fungal pathogen Candida glabrata is causing more and more problems in hospitals, as this species shows an intrinsic antifungal drug resistance or rapidly becomes resistant when challenged with antifungals. C. glabrata only grows in the yeast form, so it is lacking a yeast-to-hyphae switch, which is one of the main virulence factors of C. albicans. An important virulence factor of C. glabrata is its capacity to strongly adhere to many different substrates. To achieve this, C. glabrata expresses a large number of adhesin-encoding genes and genome comparisons with closely related species, including the non-pathogenic S. cerevisiae, which revealed a correlation between the number of adhesin-encoding genes and pathogenicity. The adhesins are involved in the first steps during an infection; they are the first point of contact with the host. For several of these adhesins, their importance in adherence to different substrates and subsequent biofilm formation was demonstrated in vitro or in vivo. In this review, we provide an overview of the role of C. glabrata adhesins during adhesion and biofilm formation both, under in vitro and in vivo conditions.

Keywords: Candida glabrata; adhesin; adhesion; biofilm.

Figure 1

Phylogenetic tree of the subphylum Saccharomycotina, including several Candida species and Saccharomyces cerevisiae. C. glabrata is more closely related to the non-pathogenic S. cerevisiae than to the pathogen C. albicans, which belongs to the CTG clade. Gabaldon and co-workers found a correlation between the number of EPA genes (Epithelial adhesin) in the genome and pathogenicity in the Nakaseomyces clade (indicated in the figure). Pathogenic species are depicted in bold (Figure adapted from [28]).

Figure 2

Schematic representation of different AFM strategies used to probe ligand binding specificities of adhesins. (A) A single C. glabrata cell can be put on the AFM cantilever to probe a certain surface, which can be made of any (hydrophobic or hydrophilic) material or coated with specific biotic substrates, such as bacterial cells or other fungal cells or even other cell types (e.g., human cell lines). (B) The cell surface of a single C. glabrata cell can be probed in three dimensions using an AFM cantilever tip to which any substrate or other single cell can be attached (Figure based on [60]). Because of all these possibilities to adapt the system, AFM is very attractive to be used in adhesion research.

Figure 3

(A) Schematic overview of the different stages of biofilm formation in C. glabrata. (B) Scanning electron microscopy picture of an in vivo mature C. glabrata biofilm on a catheter piece, which was recovered from an Intensive Care Unit (ICU) patient. The biofilm is composed of yeast cells (asterix) embedded in extracellular matrix material (m) (Figure from [76]).