title: Tuf of Streptococcus pneumoniae is a surface displayed human complement regulator binding protein.
abstract: Streptococcus pneumoniae is a Gram-positive bacterium, causing acute sinusitis, otitis media, and severe diseases such as pneumonia, bacteraemia, meningitis and sepsis. Here we identify elongation factor Tu (Tuf) as a new Factor H binding protein of S. pneumoniae. The surface protein PspC which also binds a series of other human immune inhibitors, was the first identified pneumococcal Factor H binding protein of S. pneumoniae. Pneumococcal Tuf, a 55 kDa pneumococcal moonlighting protein which is displayed on the surface of pneumococci, is also located in the cytoplasm and is detected in the culture supernatant. Tuf binds the human complement inhibitors Factor H, FHL-1, CFHR1 and also the proenzyme plasminogen. Factor H and FHL-1 bound to Tuf, retain their complement regulatory activities. Similarly, plasminogen bound to Tuf was accessible for the activator uPA and activated plasmin cleaved the synthetic chromogenic substrate S-2251 as well as the natural substrates fibrinogen and the complement proteins C3 and C3b. Taken together, Tuf of S. pneumoniae is a new multi-functional bacterial virulence factor that helps the pathogen in complement escape and likely also in ECM degradation.
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Sarbani
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Dudda
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
authors.forename: Teresia
authors.initials: T
authors.lastname: Hallström
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany; Faculty of Biology, Friedrich Schiller University, Jena, Germany. Electronic address: peter.zipfel@hki-jena.de.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D030781:Organisms, Genetically Modified; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D001426:Bacterial Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D037521:Virulence Factors; D003179:Complement C3b; D017242:Complement Factor H; D010958:Plasminogen; D010444:Peptide Elongation Factor Tu
keywords: Complement; ECM; Factor H; Plasminogen; Tuf