Stiftung Tierärztliche Hochschule Hannover (TiHo)

Homophilic protein interactions facilitate bacterial aggregation and IgG-dependent complex formation by the Streptococcus canis M protein SCM

ORCID
0000-0001-8577-2744
Affiliation
a Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine , Charité Universitätsmedizin Berlin , Berlin , Germany.
Nerlich, Andreas;
Affiliation
c Institute of Microbiology and Epizootics, Centre of Infection Medicine , Freie Universität Berlin , Berlin , Germany.
Lapschies, Antje-Maria;
ORCID
0000-0002-0530-6813
Affiliation
d Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes , University of Greifswald , Greifswald , Germany.
Kohler, Thomas P.;
Affiliation
e Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences , UC San Diego , La Jolla , CA , USA.
Cornax, Ingrid;
ORCID
0000-0002-7330-8255
Affiliation
c Institute of Microbiology and Epizootics, Centre of Infection Medicine , Freie Universität Berlin , Berlin , Germany.
Eichhorn, Inga;
Affiliation
f Infection Immunology Group, Helmholtz Centre for Infection Research , Braunschweig , Germany.
Goldmann, Oliver;
Affiliation
c Institute of Microbiology and Epizootics, Centre of Infection Medicine , Freie Universität Berlin , Berlin , Germany.
Krienke, Petra;
Affiliation
b Department of Medical Microbiology , Helmholtz Centre for Infection Research , Braunschweig , Germany.
Bergmann, Simone;
Affiliation
e Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences , UC San Diego , La Jolla , CA , USA.
Nizet, Victor;
Affiliation
d Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes , University of Greifswald , Greifswald , Germany.
Hammerschmidt, Sven;
Affiliation
b Department of Medical Microbiology , Helmholtz Centre for Infection Research , Braunschweig , Germany.
Rohde, Manfred;
Affiliation
b Department of Medical Microbiology , Helmholtz Centre for Infection Research , Braunschweig , Germany.
Fulde, Marcus

Streptococcus canis is a zoonotic agent that causes serious invasive diseases in domestic animals and humans, but knowledge about its pathogenic potential and underlying virulence mechanisms is limited. Here, we report on the ability of certain S. canis isolates to form large bacterial aggregates when grown in liquid broth. Bacterial aggregation was attributed to the presence and the self-binding activity of SCM, the M protein of S. canis, as evaluated by bacterial sedimentation assays, immunofluorescence- and electron microscopic approaches. Using a variety of truncated recombinant SCM fragments, we demonstrated that homophilic SCM interactions occur via the N-terminal, but not the C-terminal part, of the mature M protein. Interestingly, when incubated in human plasma, SCM forms soluble protein complexes comprising its known ligands, immunoglobulin G (IgG) and plasminogen (Plg). Co-incubation studies with purified host proteins revealed that SCM-mediated complex formation is based on the interaction of SCM with itself and with IgG, but not with Plg or fibrinogen (Fbg), well-established constituents of M protein-mediated protein complexes in human-associated streptococci. Notably, these soluble, SCM-mediated plasma complexes harbored complement factor C1q, which can induce complement breakdown in the periphery and therefore represent another immune evasion mechanism of SCM.

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