Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.

Abstract

Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b-binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed.

• Authors: Eric L Brown, Yasuhiro Nishiyama, Jesse W Dunkle, Shreya Aggarwal, Stephanie Planque, Kenji Watanabe, Keri Csencsits-Smith, M Gabriela Bowden, Sheldon L Kaplan, Sudhir Paul
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 13 Pg. 9940-9951 (Mar 23 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22303018 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antibodies, Catalytic
• Bacterial Proteins
• Efb protein, Staphylococcus aureus
• Immunoglobulin G
• Virulence Factors

Topics

• Adaptive Immunity (physiology)
• Adult
• Amino Acid Sequence
• Animals
• Antibodies, Bacterial (blood, immunology)
• Antibodies, Catalytic (blood, immunology)
• Bacterial Proteins
• Child
• Child, Preschool
• Female
• Humans
• Immunoglobulin G (blood, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• Protein Structure, Tertiary
• Proteolysis
• Staphylococcal Infections (blood, immunology)
• Staphylococcus aureus (immunology, pathogenicity)
• Virulence Factors (blood, immunology)