A distinct variant of the SzM protein of Streptococcus equi subsp. zooepidemicus recruits C1q independent of IgG binding and inhibits activation of the classical complement pathway.
Abstract: Streptococcus equi subsp. zooepidemicus (SEZ) is a major equine pathogen that causes pneumonia, abortion, and polyarthritis. It can also cause invasive infections in humans. SEZ expresses the M-like protein SzM, which recruits host proteins such as fibrinogen to the bacterial surface. Equine SEZ strain C2, which binds only comparably low amounts of human fibrinogen in comparison to human SEZ strain C33, was previously shown to proliferate in equine and human blood. As the expression of SzM_C2 was necessary for survival in blood, this study investigated the working hypothesis that SzM_C2 inhibits complement activation through a mechanism other than fibrinogen and non-immune immunoglobulin binding. Loss-of-function experiments showed that SEZ C2, but not C33, binds C1q via SzM in IgG-free human plasma. Furthermore, SzM C2 expression is necessary for recruiting purified human or equine C1q to the bacterial surface. Flow cytometry analysis demonstrated that SzM expression in SEZ C2 is crucial for the significant reduction of C3b labelling in human plasma. Addition of human plasma to immobilized rSzM_C2 and immobilized aggregated IgG led to binding of C1q, but only the latter activated the complement system, as shown by the detection of C4 deposition. Complement activation induced by aggregated IgG was significantly reduced if human plasma was pre-incubated with rSzM_C2. Furthermore, rSzM_C2, but not rSzM_C33, inhibited the activation of the classical complement pathway in human plasma, as determined in an erythrocyte lysis experiment. In conclusion, the immunoglobulin-independent binding of C1q to SzM_C2 is associated with complement inhibition.
Publication Date: 2023-07-14 PubMed ID: 37450582PubMed Central: PMC10351459DOI: 10.1080/21505594.2023.2235461Google Scholar: Lookup
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Summary
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Researchers have identified that the SzM protein variant in the particular strain of bacteria, Streptococcus equi subsp. zooepidemicus (SEZ), found in horses can recruit a molecule called C1q while inhibiting the activation of the classical complement system, a part of the immune system, without needing to bind with immunoglobulin (antibodies). This mechanism contributes to the survival of the bacteria in both equine and human blood, demonstrating a unique ability to evade the host’s immune response.
Background of the Study
- SEZ is a clinically significant bacteria causing respiratory diseases, abortion, and polyarthritis in horses. It’s also been found to cause invasive infections in humans.
- The study centered around the protein SzM, expressed by SEZ, which recruits other proteins like fibrinogen, to the bacterial surface, aiding in its survival.
The Experiment
- The experiment focused on two strains of SEZ, strain C2 found in horses and strain C33 found in humans.
- In previous studies, SEZ strain C2 had shown the ability to proliferate in equine and human blood, with SzM_C2 protein playing a crucial role in its survival. This led to the working hypothesis of the current research.
- The researchers speculated SzM_C2 might have a mechanism for inhibiting the activation of the immune response in the host, independent of binding with immunoglobulins or fibrinogen.
Results of the Experiment
- Through loss-of-function experiments, it was found that SEZ C2, unlike C33, could bind with C1q (part of the complement system of the immune response) without needing to bind with IgG, a type of immunoglobulin, in human plasma.
- This indicates that SzM_C2 prevents activation of the host’s immune response by binding with C1q, a critical molecule in activating the classical pathway of the complement system.
- Flow cytometry analysis showed that expression of SzM in SEZ C2 significantly reduced C3b (another protein in the complement system) labeling in human plasma, signifying inhibited complement activation.
- Furthermore, rSzM_C2, but not rSzM_C33, inhibited the activation of the classical complement pathway in human plasma.
Conclusion
- The study concludes that the unique ability of SzM_C2 to bind with C1q independently of immunoglobulin is associated with complement inhibition, aiding in the survival of SEZ C2 strain in both equine and human blood.
Cite This Article
APA
Bergmann R, Schroedl W, Müller U, Baums CG.
(2023).
A distinct variant of the SzM protein of Streptococcus equi subsp. zooepidemicus recruits C1q independent of IgG binding and inhibits activation of the classical complement pathway.
Virulence, 14(1), 2235461.
https://doi.org/10.1080/21505594.2023.2235461 Publication
Researcher Affiliations
- Institute of Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
- Institute of Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
- Institute of Immunology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
- Institute of Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
MeSH Terms
- Animals
- Horses
- Humans
- Streptococcus equi / genetics
- Streptococcus equi / metabolism
- Complement C1q / metabolism
- Complement Pathway, Classical
- Complement Activation
- Fibrinogen
- Immunoglobulins
Conflict of Interest Statement
No potential conflict of interest was reported by the author(s).
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