title: SCM, the M Protein ofStreptococcus canisBinds Immunoglobulin G.
abstract: The M protein ofStreptococcus canis(SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particularS. canisisolate to bind to IgG significantly correlates with ascm-positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG bindingS. gordoniiand Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from differentS. canisisolates but differs significantly from IgG-Fc receptors ofS. pyogenesandS. dysgalactiaesub.equisimilis, respectively. In summary, we present an additional role of SCM in the pathogen-host interaction ofS. canis. The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.
authors.affiliation: Department of Medical Microbiology, Helmholtz Center for Infection Research Braunschweig, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.affiliation: Institute of Microbiology and Epizootics, Centre for Infection Medicine, Freie Universität Berlin Berlin, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Eichhorn
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt Universität Greifswald Greifswald, Germany.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kohler
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt Universität Greifswald Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Department of Infection Immunology, Helmholtz Center for Infection Research Braunschweig, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Goldmann
authors.affiliation: Central Facility for Microscopy, Helmholtz Center for Infection Research Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Department of Medical Microbiology, Helmholtz Center for Infection ResearchBraunschweig, Germany; Institute of Microbiology and Epizootics, Centre for Infection Medicine, Freie Universität BerlinBerlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002415:Cats; D002417:Cattle; D003001:Cloning, Molecular; D004285:Dogs; D006041:Goats; D006736:Horses; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G / Q000276:immunology*; D010802:Phylogeny; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins; D013291:Streptococcus / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism; D015047:Zoonoses
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D037521:Virulence Factors; C014689:streptococcal M protein
keywords: Immunoglobulin G; M protein; Streptococcus canis; anti-phagocytic activity; zoonosis