title: Haemophilus influenzae uses the surface protein E to acquire human plasminogen and to evade innate immunity.
abstract: Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen-PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655Δpe) bound plasminogen with ∼65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia coli also bound plasminogen. Plasminogen, either attached to intact H. influenzae or bound to PE, was accessible for urokinase plasminogen activator. The converted active plasmin cleaved the synthetic substrate S-2251, and the natural substrates fibrinogen and C3b. Using synthetic peptides that cover the complete sequence of the PE protein, the major plasminogen-binding region was localized to a linear 28-aa-long N-terminal peptide, which represents aa 41-68. PE binds plasminogen and also vitronectin, and the two human plasma proteins compete for PE binding. Thus, PE is a major plasminogen-binding protein of the Gram-negative bacterium H. influenzae, and when converted to plasmin, PE-bound plasmin aids in immune evasion and contributes to bacterial virulence.
authors: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Jena, Germany.
authors: Diana
authors: D
authors: Barthel
authors: Birendra
authors: B
authors: Singh
authors: Kristian
authors: K
authors: Riesbeck
authors: Peter F
authors: PF
authors: Zipfel
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D003179:Complement C3b / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010958:Plasminogen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D059748:Proteolysis; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019096:Vitronectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D010455:Peptides; D037521:Virulence Factors; D019096:Vitronectin; D003179:Complement C3b; D005340:Fibrinogen; D010958:Plasminogen