Heterologous Expression of Candida albicans Cell Wall-Associated Adhesins in Saccharomyces cerevisiae Reveals Differential Specificities in Adherence and Biofilm Formation and in Binding Oral Streptococcus gordonii

Colonization and infection of the human host by opportunistic pathogenCandida albicans derive from an ability of this fungus to colonize mucosal tissues and prosthetic devices within the polymicrobial communities present. To determine the functions ofC. albicans cell wall proteins in interactions with host or bacterial molecules,Saccharomyces cerevisiae was utilized as a surrogate host to expressC. albicans cell wall proteins Als3p, Eap1p, Hwp1p, and Rbt1p. Salivary pellicle and fibrinogen were identified as novel substrata for Als3p and Hwp1p, while only Als3p mediated adherence ofS. cerevisiae to basement membrane collagen type IV. ParentalS. cerevisiae cells failed to form biofilms on salivary pellicle, polystyrene, or silicone, but cells expressing Als3p or Hwp1p exhibited significant attachment to each surface. Virulence factor Rbt1p also conferred lower-level binding to salivary pellicle and polystyrene.S. cerevisiae cells expressing Eap1p formed robust biofilms upon polystyrene surfaces but not salivary pellicle. Proteins Als3p and Eap1p, and to a lesser degree Hwp1p, conferred uponS. cerevisiae the ability to bind cells of the oral primary colonizing bacteriumStreptococcus gordonii . These interactions, which occurred independently of amyloid aggregate formation, provide the first examples of specificC. albicans surface proteins serving as receptors for bacterial adhesins.Streptococcus gordonii did not bind parentalS. cerevisiae or cells expressing Rbt1p. Taken collectively, these data suggest that a network of cell wall proteins comprising Als3p, Hwp1p, and Eap1p, with complementary adhesive functions, promotes interactions ofC. albicans with host and bacterial molecules, thus leading to effective colonization within polymicrobial communities.