Overexpression of theCandida albicans ALA1Gene inSaccharomyces cerevisiaeResults in Aggregation following Attachment of Yeast Cells to Extracellular Matrix Proteins, Adherence Properties Similar to Those ofCandida albicans

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Abstract
Candida albicansmaintains a commensal relationship with human hosts, probably by adhering to mucosal tissue in a variety of physiological conditions. We show that adherence due to theC. albicansgeneALA1when transformed intoSaccharomyces cerevisiae, is comprised of two sequential steps. Initially,C. albicansrapidly attaches to extracellular matrix (ECM) protein-coated magnetic beads in small numbers (the attachment phase). This is followed by a relatively slower step in which cell-to-cell interactions predominate (the aggregation phase). Neither of these phases is observed inS. cerevisiae. However, expression of theC. albicans ALA1gene from a low-copy vector causesS. cerevisiaetransformants to attach to ECM-coated magnetic beads without appreciable aggregation. Expression ofALA1from a high-copy vector results in both attachment and aggregation. Moreover, transcriptional fusion ofALA1with the galactose-inducible promoters GALS, GALL, and GAL1, allowing for low, moderate, and high levels of inducible transcription, respectively, causes attachment and aggregation that correlates with the strength of the GAL promoter. The adherence ofC. albicansandS. cerevisiaeoverexpressingALA1to a number of protein ligands occurs over a broad pH range, is resistant to shear forces generated by vortexing, and is unaffected by the presence of sugars, high salt levels, free ligands, or detergents. Adherence is, however, inhibited by agents that disrupt hydrogen bonds. The similarities in the adherence and aggregation properties ofC. albicansandS. cerevisiaeoverexpressingALA1suggest a role in adherence and aggregation forALA1andALA1-like genes inC. albicans.