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Common protective antigens of group A streptococcal M proteins masked by fibrinogen
Abstract:
The influence of fibrinogen on the opsonization of Group A streptococci by type-specific and cross-reactive anti-M protein antisera was investigated. As previously reported for type 24 streptococci, fibrinogen inhibited the complement-mediated opsonization of types 5, 6, and 19 organisms. Rabbit antisera against large peptide fragments of purified homologous M proteins (pep M proteins) overcame the anti-opsonic effect of fibrinogen in a dose-dependent manner. In the presence of optimal amounts of antibody, bacterial uptake by PMN was equal in serum and plasma, and greater than could be obtained in serum in the absence of antibody. Polyclonal anti-pep M sera contained antibodies directed against fibrinogen-binding as well as fibrinogen-nonbinding sites or regions of the M protein molecule. Three cross-reactive anti-pep M sera included antibodies directed against fibrinogen binding sites or regions of the cross-reacting M proteins. In the two sera studied in detail, these antibodies accounted for a large part of the cross-reacting anti-M antibody present in the sera. We suggest that fibrinogen binding sites on different serotypes of M protein may be structurally and therefore antigenically similar. Conservation of fibrinogen binding sites on M proteins may be related to their protective anti-opsonic function.
Insights
Fibrinogen hinders Group A Streptococcus opsonization, but antibodies targeting M protein fragments can reverse this effect. This suggests conserved fibrinogen-binding sites on M proteins contribute to bacterial immune evasion.
Area of Science:
- Immunology
- Microbiology
- Bacteriology
Background:
- Group A Streptococcus (GAS) M protein is a key virulence factor.
- M protein mediates bacterial resistance to phagocytosis through opsonization.
- Fibrinogen is known to inhibit complement-mediated opsonization of certain GAS serotypes.
Purpose of the Study:
- To investigate the role of fibrinogen in inhibiting the opsonization of GAS by specific and cross-reactive anti-M protein antibodies.
- To determine if antibodies targeting M protein fragments can overcome fibrinogen's anti-opsonic effect.
- To explore the antigenic similarity of fibrinogen-binding sites on different M protein serotypes.
Main Methods:
- Investigated the influence of fibrinogen on GAS opsonization using type-specific and cross-reactive anti-M protein antisera.
- Utilized rabbit antisera against purified M protein fragments (pep M proteins).
- Quantified bacterial uptake by polymorphonuclear leukocytes (PMN) in serum and plasma.
Main Results:
- Fibrinogen inhibited complement-mediated opsonization of GAS types 5, 6, and 19.
- Antibodies against M protein fragments (pep M proteins) dose-dependently overcame fibrinogen's anti-opsonic effect.
- In the presence of optimal antibodies, bacterial uptake by PMN was significantly enhanced.
- Anti-pep M sera contained antibodies against both fibrinogen-binding and non-binding M protein regions.
- Cross-reactive anti-pep M sera showed antibodies targeting fibrinogen-binding sites, suggesting conserved structures.
Conclusions:
- Fibrinogen binding sites on different M protein serotypes are likely structurally and antigenically similar.
- The conservation of these fibrinogen-binding sites may be crucial for M protein's function in evading the host immune system.
- Targeting these conserved sites with antibodies could be a strategy to enhance bacterial clearance.