RRC ID 77494
Author Terao Y, Yamaguchi M, Hamada S, Kawabata S.
Title Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils.
Journal J Biol Chem
Abstract Streptococcus pyogenes is an important pathogen that causes pharyngitis, sepsis, and rheumatic fever. Cell-associated streptococcal C5a peptidase (ScpA) protects S. pyogenes from phagocytosis and has been suggested to interrupt host defenses by enzymatically cleaving complement C5a, a major factor in the accumulation of neutrophils at sites of infection. How S. pyogenes recognizes and binds to C5a, however, is unclear. We detected a C5a-binding protein in 8 M urea extracts of S. pyogenes by ligand blotting using biotinylated C5a. Searching of genome databases showed that the C5a-binding protein is identical to the streptococcal plasmin receptor (Plr), also known as streptococcal surface dehydrogenase (SDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the present study we identified a novel function of this multifunctional protein. Western blotting and immunofluorescence microscopy with anti-Plr/SDH/GAPDH showed that Plr/SDH/GAPDH is located on the bacterial surface and released into the culture supernatant. Next, we examined whether the streptococcal Plr/SDH/GAPDH inhibits the biological effects of C5a on human neutrophils. We found that soluble Plr/SDH/GAPDH inhibits C5a-activated chemotaxis and H2O2 production. Furthermore, our results suggested that soluble Plr/SDH/GAPDH captures C5a, inhibiting its chemotactic function. Also, cell-associated Plr/SDH/GAPDH and ScpA were both necessary for the cleavage of C5a on the bacterial surface. Together, these results indicate that the multifunctional protein Plr/SDH/GAPDH has additional functions that help S. pyogenes escape detection by the host immune system.
Volume 281(20)
Pages 14215-23
Published 2006-5-19
DOI 10.1074/jbc.M513408200
PII S0021-9258(20)78065-8
PMID 16565520
MeSH Animals Base Sequence Biotinylation Chemotaxis Complement C5a / chemistry Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / chemistry* Humans Ligands Molecular Sequence Data Neutrophils / microbiology* Protein Binding Rabbits Receptors, Peptide / chemistry Streptococcus pyogenes / enzymology*
IF 4.238
Human and Animal Cells Hep-G2