title: Functional regions of Candida albicans hyphal cell wall protein Als3 that determine interaction with the oral bacterium Streptococcus gordonii.
abstract: The opportunistic pathogen Candida albicans colonizes the oral cavity and gastrointestinal tract. Adherence to host cells, extracellular matrix and salivary glycoproteins that coat oral surfaces, including prostheses, is an important prerequisite for colonization. In addition, interactions of C. albicans with commensal oral streptococci are suggested to promote retention and persistence of fungal cells in mixed-species communities. The hyphal filament specific cell wall protein Als3, a member of the Als protein family, is a major determinant in C. albicans adherence. Here, we utilized site-specific in-frame deletions within Als3 expressed on the surface of heterologous Saccharomyces cerevisiae to determine regions involved in interactions of Als3 with Streptococcus gordonii. N-terminal region amino acid residue deletions Δ166-225, Δ218-285, Δ270-305 and Δ277-286 were each effective in inhibiting binding of Strep. gordonii to Als3. In addition, these deletions differentially affected biofilm formation, hydrophobicity, and adherence to silicone and human tissue proteins. Deletion of the central repeat domain (Δ434-830) did not significantly affect interaction of Als3 with Strep. gordonii SspB protein, but affected other adherence properties and biofilm formation. Deletion of the amyloid-forming region (Δ325-331) did not affect interaction of Als3 with Strep. gordonii SspB adhesin, suggesting this interaction was amyloid-independent. These findings highlighted the essential function of the N-terminal domain of Als3 in mediating the interaction of C. albicans with S. gordonii, and suggested that amyloid formation is not essential for the inter-kingdom interaction.
authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK.
authors.forename: Caroline V
authors.initials: CV
authors.lastname: Bamford
authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Nobbs
authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK.
authors.forename: Michele E
authors.initials: ME
authors.lastname: Barbour
authors.affiliation: School of Dentistry, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lamont
authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, UK.
authors.forename: Howard F
authors.initials: HF
authors.lastname: Jenkinson
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D018441:Biofilms; D002176:Candida albicans / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D009055:Mouth / Q000382:microbiology*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D054773:Streptococcus gordonii / Q000502:physiology*
chemical_list: C113620:ALS3 protein, Candida albicans; D018829:Adhesins, Bacterial; D016326:Extracellular Matrix Proteins; D005656:Fungal Proteins; C068465:salivary agglutinin receptor, Streptocococcus