Abstract
ABSTRACTStreptococcus 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.
Highlights
Streptococcus canis is a frequent colonizer of mucosal surfaces and the skin of dogs and cats, and occasionally identified in various other host species such as cows, rats, minks, mice, rabbits, and foxes [1,2,3,4,5,6]
We recently described how SCM binds immunoglobulin G (IgG) in a non-opsonic manner and found that this interaction prevents the deposition of C1q, a primary component of the classical complement activation pathway, on the bacterial surface [23]
The mechanisms by which M proteins facilitate anti-phagocytosis are versatile and include interactions with the host immune system and the ability to interact with itself
Summary
Streptococcus canis is a frequent colonizer of mucosal surfaces and the skin of dogs and cats, and occasionally identified in various other host species such as cows, rats, minks, mice, rabbits, and foxes [1,2,3,4,5,6]. S. canis can be transmitted among different host species suggesting a certain zoonotic potential [11,12,13,14,15,16]. Streptococcal M proteins are important virulence factors that confer anti-phagocytic properties, but may contribute to the development of post-streptococcal (autoimmune) sequelae [17,18]. S. canis was long considered to be “M protein negative”, since very few epidemiological studies reported about the identification of emmtypeable S. canis isolates [19,20]. We recently identified an open reading frame in a zoonotic strain of
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