title: Evaluation of the role of Candida albicans agglutinin-like sequence (Als) proteins in human oral epithelial cell interactions.
abstract: The fungus C. albicans uses adhesins to interact with human epithelial surfaces in the processes of colonization and pathogenesis. The C. albicans ALS (agglutinin-like sequence) gene family encodes eight large cell-surface glycoproteins (Als1-Als7 and Als9) that have adhesive function. This study utilized C. albicans Δals mutant strains to investigate the role of the Als family in oral epithelial cell adhesion and damage, cytokine induction and activation of a MAPK-based (MKP1/c-Fos) signaling pathway that discriminates between yeast and hyphae. Of the eight Δals mutants tested, only the Δals3 strain showed significant reductions in oral epithelial cell adhesion and damage, and cytokine production. High fungal:epithelial cell multiplicities of infection were able to rescue the cell damage and cytokine production phenotypes, demonstrating the importance of fungal burden in mucosal infections. Despite its adhesion, damage and cytokine induction phenotypes, the Δals3 strain induced MKP1 phosphorylation and c-Fos production to a similar extent as control cells. Our data demonstrate that Als3 is involved directly in epithelial adhesion but indirectly in cell damage and cytokine induction, and is not the factor targeted by oral epithelial cells to discriminate between the yeast and hyphal form of C. albicans.
authors.affiliation: Department of Oral Immunology, King's College London Dental Institute, King's College London, London, United Kingdom. celia.murciano@kcl.ac.uk
authors.forename: Celia
authors.initials: C
authors.lastname: Murciano
authors.forename: David L
authors.initials: DL
authors.lastname: Moyes
authors.forename: Manohursingh
authors.initials: M
authors.lastname: Runglall
authors.forename: Priscila
authors.initials: P
authors.lastname: Tobouti
authors.forename: Ayesha
authors.initials: A
authors.lastname: Islam
authors.forename: Lois L
authors.initials: LL
authors.lastname: Hoyer
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
mesh_terms: D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology* / Q000473:pathology; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C113620:ALS3 protein, Candida albicans; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005656:Fungal Proteins; D016760:Proto-Oncogene Proteins c-fos; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1