Reference: Poltermann S, et al. (2007) Gpm1p Is a Factor H-, FHL-1-, and Plasminogen-binding Surface Protein of Candida albicans. J Biol Chem 282(52):37537-44

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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 SCRs 6-7 and Factor H utilizes two contact regions which are located in SCRs 6-7 and in SCRs 19-20. In addition, recombinant CaGpm1p binds plasminogen via lysine residues and three linear, internal plasminogen-binding regions were identified using a peptide-spot assay. CaGpm1p is a surface protein as demonstrated by immunostaining and flow cytometry. A C. albicans gpm1-/- mutant strain was generated which did not grow on glucose supplemented, but on ethanol and glycerol supplemented media. 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 uPA to proteolytically active plasmin. Thus the surface-expressed CaGpm1p is a virulence factor, which utilizes the host Factor H, FHL-1 and plasminogen for immune evasion and degradation of extracellular matrices.

Reference Type
Journal Article
Authors
Poltermann S, Kunert A, von der Heide M, Eck R, Hartmann A, Zipfel PF
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