title: Glycosylphosphatidylinositol-anchored proteases of Candida albicans target proteins necessary for both cellular processes and host-pathogen interactions.
abstract: Intracellular and secreted proteases fulfill multiple functions in microorganisms. In pathogenic microorganisms extracellular proteases may be adapted to interactions with host cells. Here we describe two cell surface-associated aspartic proteases, Sap9 and Sap10, which have structural similarities to yapsins of Saccharomyces cerevisiae and are produced by the human pathogenic yeast Candida albicans. Sap9 and Sap10 are glycosylphosphatidylinositol-anchored and located in the cell membrane or the cell wall. Both proteases are glycosylated, cleave at dibasic or basic processing sites similar to yapsins and Kex2-like proteases, and have functions in cell surface integrity and cell separation during budding. Overexpression of SAP9 in mutants lacking KEX2 or SAP10, or of SAP10 in mutants lacking KEX2 or SAP9, only partially restored these phenotypes, suggesting distinct target proteins of fungal origin for each of the three proteases. In addition, deletion of SAP9 and SAP10 modified the adhesion properties of C. albicans to epithelial cells and caused attenuated epithelial cell damage during experimental oral infection suggesting a unique role for these proteases in both cellular processes and host-pathogen interactions.
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Albrecht
authors.forename: Angelika
authors.initials: A
authors.lastname: Felk
authors.forename: Iva
authors.initials: I
authors.lastname: Pichova
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Piet
authors.initials: P
authors.lastname: de Groot
authors.forename: Donna
authors.initials: D
authors.lastname: Maccallum
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schäfer
authors.forename: Frans
authors.initials: F
authors.lastname: Klis
authors.forename: Michel
authors.initials: M
authors.lastname: Monod
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism / Q000502:physiology*; D002176:Candida albicans / Q000378:metabolism* / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D016253:Microscopy, Immunoelectron; D009154:Mutation; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D005656:Fungal Proteins; D017261:Glycosylphosphatidylinositols; D010455:Peptides; D011994:Recombinant Proteins; D002686:Chitin; D049452:Green Fluorescent Proteins; D016282:Aspartic Acid Endopeptidases; C116371:Sap9 protein, Candida albicans; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase