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Acquisition of regulators of complement activation by Streptococcus pyogenes serotype M1
Vinod Pandiripally1, Eugene Gregory, David Cue
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Infection and Immunity
|October 16, 2002
Summary
Streptococcus pyogenes uses the Fba protein to evade immune responses by binding complement regulators factor H (FH) and FH-like protein 1 (FHL-1). This binding inhibits opsonization and phagocytosis, aiding bacterial survival.
Area of Science:
- Immunology
- Microbiology
- Bacteriology
Background:
- Opsonization by complement proteins is crucial for bacterial clearance.
- Streptococcus pyogenes employs mechanisms to evade complement-mediated opsonization.
- Binding of human complement regulators like factor H (FH) and FH-like protein 1 (FHL-1) is a key evasion strategy.
Purpose of the Study:
- To investigate the role of the S. pyogenes cell surface protein Fba in binding complement regulators FH and FHL-1.
- To determine the contribution of Fba to immune evasion, specifically resistance to phagocytosis and complement deposition.
Main Methods:
- Construction and analysis of S. pyogenes mutant strains lacking Fba, M1 protein, or both.
- Assays for FH binding, C3 deposition, and susceptibility to phagocytosis.
- Plasma adsorption experiments and bacterial culture with protease inhibitors (E64) to study protein regulation.
Main Results:
- The S. pyogenes protein Fba mediates the binding of FH and FHL-1.
- Fba expression is sufficient for binding FH and FHL-1 from human plasma.
- Fba contributes to bacterial survival in human blood by inhibiting C3 deposition and reducing phagocytosis.
Conclusions:
- Fba is an antiopsonic and antiphagocytic protein in Streptococcus pyogenes.
- Cell surface proteolysis appears to regulate Fba expression and function.
- Fba represents a novel target for understanding and combating S. pyogenes infections.