SCM, a novel M-like protein from<i>Streptococcus canis</i>, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration

Fulde, Marcus; Rohde, Manfred; Hitzmann, Angela; Preissner, Klaus T.; Nitsche-Schmitz, D. Patric; Nerlich, Andreas; Chhatwal, Gursharan S.; Bergmann, Simone

doi:10.1042/bj20101121

Cited by 38 publications

(76 citation statements)

References 52 publications

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“…This would explain the recent finding that some S canis do not bind the protein (Fulde and others 2011). Nine S canis from healthy cats expressed type 4 ScM alleles, the amino acid sequence of which showed near identity with other types.…”

Section: Discussionmentioning

confidence: 89%

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Biotypes and ScM types of isolates of Streptococcus canis from diseased and healthy cats

et al. 2017

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Lancefield group G is a component of the normal urogenital and pharyngeal flora of the cat. It is also frequently implicated in epizootics of severe disease in closed cat colonies and animal shelters. Given the importance of as a feline pathogen and relative lack of published information on characteristics potentially associated with virulence, the authors have compared isolates from healthy and diseased cats in New York and California using fermentation profiles (biotype) and ScM sequences. With few exceptions, isolates associated with disease were biotype 1. Four alleles of were identified of which type 1 dominated in diseased cats. Type 4 allelic variants were found only in healthy cats and all but one were biotype 2. Type 2 and 3 alleles showed extensive N-terminal variation suggesting a plasminogen-binding site as found on the type 1 allele was absent. Cat antisera to ScM were opsonobactericidal, and these potentially protective antibodies increased during convalescence.

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Section: Discussionmentioning

confidence: 89%

“…The SzM protein of virulent S. zooepidemicus NC78 was shown to bind plasminogen. A protein designated ScM with similar plasminogen binding activity has been identified on 13 of 19 S canis isolates of canine origin in Europe (Fulde and others 2011). ScM-negative isolates showed greatly reduced binding of plasminogen.…”

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confidence: 99%

Biotypes and ScM types of isolates of Streptococcus canis from diseased and healthy cats

et al. 2017

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“…Lpd attaches plasminogen via a major binding site localized in kringle domain 4. Streptococcal surface protein PAM binds human plasminogen via kringle domain 2, and the Streptococcus canis protein SCM binds plasminogen via kringle domain 5 (53,54). Thus, the three bacterial proteins bind to different kringle domains of plasminogen.…”

Section: Discussionmentioning

confidence: 99%

Dihydrolipoamide Dehydrogenase of Pseudomonas aeruginosa Is a Surface-Exposed Immune Evasion Protein That Binds Three Members of the Factor H Family and Plasminogen

Hallström

Mörgelin

Barthel

et al. 2012

The Journal of Immunology

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The opportunistic human pathogen Pseudomonas aeruginosa causes a wide range of diseases. To cross host innate immune barriers, P. aeruginosa has developed efficient strategies to escape host complement attack. In this study, we identify the 57-kDa dihydrolipoamide dehydrogenase (Lpd) as a surface-exposed protein of P. aeruginosa that binds the four human plasma proteins, Factor H, Factor H-like protein-1 (FHL-1), complement Factor H-related protein 1 (CFHR1), and plasminogen. Factor H contacts Lpd via short consensus repeats 7 and 18–20. Factor H, FHL-1, and plasminogen when bound to Lpd were functionally active. Factor H and FHL-1 displayed complement-regulatory activity, and bound plasminogen, when converted to the active protease plasmin, cleaved the chromogenic substrate S-2251 and the natural substrate fibrinogen. The lpd of P. aeruginosa is a rather conserved gene; a total of 22 synonymous and 3 nonsynonymous mutations was identified in the lpd gene of the 5 laboratory strains and 13 clinical isolates. Lpd is surface exposed and contributes to survival of P. aeruginosa in human serum. Bacterial survival was reduced when Lpd was blocked on the surface prior to challenge with human serum. Similarly, bacterial survival was reduced up to 84% when the bacteria was challenged with complement active serum depleted of Factor H, FHL-1, and CFHR1, demonstrating a protective role of the attached human regulators from complement attack. In summary, Lpd is a novel surface-exposed virulence factor of P. aeruginosa that binds Factor H, FHL-1, CFHR1, and plasminogen, and the Lpd-attached regulators are relevant for innate immune escape and most likely contribute to tissue invasion.

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“…Hitzmann and co-workers described the Arginine Deiminase System in S. canis , which confers resistance against acidic conditions, as found in the host cell phagolysosome (Hitzmann et al, 2013). Finally, we previously identified a surface-associated protein with structural and functional, but not genetic similarities to the M protein family of streptococci, which we therefore designated SCM for S. canis M protein (Fulde et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

“…Plg is a zymogen for the broad-spectrum serine protease plasmin. Although S. canis is not able to intrinsically activate Plg, plasmin can be immobilized onto the bacterial surface via SCM, where its enzymatic activity can degrade fibrinogen and aggregate fibrin thrombi (Fulde et al, 2011, 2013a,b). Plasmin mediated tissue degradation is an important virulence trait of disseminative streptococcal infections (Sun et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G

Bergmann

Eichhorn

Kohler

et al. 2017

Front. Cell. Infect. Microbiol.

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The M protein of Streptococcus 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 particular S. canis isolate to bind to IgG significantly correlates with a scm-positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and 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 different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis, respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. 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.

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SCM, a novel M-like protein fromStreptococcus canis, binds (mini)-plasminogen with high affinity and facilitates bacterial transmigration

Cited by 38 publications

References 52 publications

Biotypes and ScM types of isolates of Streptococcus canis from diseased and healthy cats

Biotypes and ScM types of isolates of Streptococcus canis from diseased and healthy cats

Dihydrolipoamide Dehydrogenase of Pseudomonas aeruginosa Is a Surface-Exposed Immune Evasion Protein That Binds Three Members of the Factor H Family and Plasminogen

SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G

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