title: Gpm1p is a factor H-, FHL-1-, and plasminogen-binding surface protein of Candida albicans.
abstract: The human pathogenic yeast Candida albicans utilizes host complement regulators for immune evasion. Here we identify the first fungal protein that binds Factor H and FHL-1. By screening a protein array of 4088 proteins of Saccharomyces cerevisiae, phosphoglycerate mutase (ScGpm1p) was identified as a Factor H- and FHL-1-binding protein. The homologous C. albicans Gpm1p (CaGpm1p) was cloned and recombinantly expressed as a 36-kDa His-tagged protein. Purified CaGpm1p binds the host complement regulators Factor H and FHL-1, but not C4BP. The CaGpm1p binding regions in the host proteins were localized; FHL-1 binds via short consensus repeats (SCRs) 6 and 7, and Factor H utilizes two contact regions that are located in SCRs 6 and 7 and in SCRs 19 and 20. In addition, recombinant CaGpm1p binds plasminogen via lysine residues. CaGpm1p is a surface protein as demonstrated by immunostaining and flow cytometry. A C. albicans gpm1(-/-) mutant strain was generated that did not grow on glucose-supplemented but on ethanol- and glycerol-supplemented medium. Reduced binding of Factor H and plasminogen to the null mutant strain is in agreement with the presence of additional binding proteins. Attached to CaGpm1p, each of the three host plasma proteins is functionally active. Factor H and FHL-1 show cofactor activity for cleavage of C3b, and bound plasminogen is converted by urokinase-type plasminogen activator to proteolytically active plasmin. Thus, the surface-expressed CaGpm1p is a virulence factor that utilizes the host Factor H, FHL-1, and plasminogen for immune evasion and degradation of extracellular matrices.
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, 07745, Jena, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Poltermann
authors.forename: Anja
authors.initials: A
authors.lastname: Kunert
authors.forename: Monika
authors.initials: M
authors.lastname: von der Heide
authors.forename: Raimund
authors.initials: R
authors.lastname: Eck
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartmann
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
mesh_terms: D002176:Candida albicans / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000737:chemistry; D005341:Fibrinolysin / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry* / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry; D008954:Models, Biological; D010736:Phosphoglycerate Mutase / Q000737:chemistry / Q000502:physiology*; D010958:Plasminogen / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D037521:Virulence Factors / Q000737:chemistry / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D000431:Ethanol; D010958:Plasminogen; D005341:Fibrinolysin; C526914:Gpm1 protein, Candida albicans; D010736:Phosphoglycerate Mutase; D005947:Glucose; D005990:Glycerol