title: Identification of a novel host-specific IgG protease in Streptococcus phocae subsp. phocae.
abstract: Streptococcus (S.) phocae subsp. phocae causes bronchopneumonia and septicemia in a variety of marine mammals. Especially in harbor seals infected with phocine distemper virus it plays an important role as an opportunistic pathogen. This study was initiated by the detection of IgG cleavage products in Western blot analysis after incubation of bacterial supernatant with harbor seal serum. Hence, the objectives of this study were the identification and characterization of a secreted IgG cleaving protease in S. phocae subsp. phocae isolated from marine mammals. To further identify the responsible factor of IgG cleavage a protease inhibitor profile was generated. Inhibition of the IgG cleaving activity by iodoacetamide and Z-LVG-CHN2indicated that a cysteine protease is involved. Moreover, an anti-IdeS antibody directed against the IgG endopeptidase IdeS of S. pyogenes showed cross reactivity with the putative IgG protease of S. phocae subsp. phocae. The IgG cleaving factor of S. phocae subsp. phocae was identified through an inverse PCR approach and designated IdeP (Immunoglobulin G degrading enzyme of S. phocae subsp. phocae) in analogy to the cysteine protease IdeS. Notably, recombinant (r) IdeP is a host and substrate specific protease as it cleaves IgG from grey and harbor seals but not IgG from harbor porpoises or non-marine mammals. The identification of IdeP represents the first description of a protein in S. phocae subsp. phocae involved in immune evasion. Furthermore, the fact that IdeP cleaves solely IgG of certain marine mammals reflects functional adaption of S. phocae subsp. phocae to grey and harbor seals as its main hosts.
authors.affiliation: Institute for Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, University Leipzig, Leipzig, Germany. Electronic address: viktoria.rungelrath@uni-leipzig.de.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Rungelrath
authors.affiliation: Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany. Electronic address: jan.wohlsein@arcor.de.
authors.forename: Jan Christian
authors.initials: JC
authors.lastname: Wohlsein
authors.affiliation: Institute for Terrestrial and Aquatic Wildlife Research of the University of Veterinary Medicine Hannover, Büsum, Germany. Electronic address: ursula.siebert@tiho-hannover.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Siebert
authors.affiliation: Pathology, Microbiology and Immunology, Veterinary Medicine, UC Davis, United States. Electronic address: jlstott@ucdavis.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stott
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig-University Giessen, Giessen, Germany. Electronic address: Ellen.Prenger-Berninghoff@vetmed.uni-giessen.de.
authors.forename: Ellen
authors.initials: E
authors.lastname: Prenger-Berninghoff
authors.affiliation: Department of Molecular Biology and Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden. Electronic address: Ulrich.von-Pawel@molbiol.umu.se.
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Pawel-Rammingen
authors.affiliation: Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany. Electronic address: Peter.Valentin@tiho-hannover.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Valentin-Weigand
authors.affiliation: Institute for Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, University Leipzig, Leipzig, Germany; Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany. Electronic address: christoph.baums@vetmed.uni-leipzig.de.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Baums
authors.affiliation: Institute for Microbiology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany. Electronic address: jana_seele@gmx.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Seele
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D058507:Host Specificity; D057131:Immune Evasion; D007074:Immunoglobulin G / Q000378:metabolism*; D007460:Iodoacetamide / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D046049:Phoca / Q000382:microbiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins; D017422:Sequence Analysis, DNA / Q000662:veterinary; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; C062355:N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethane; D010450:Endopeptidases; D007460:Iodoacetamide
keywords: IdeS; Immunoglobulin degrading protease; Marine mammals; Streptococcus phocae