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The Pneumococcal Surface Proteins PspA and PspC Sequester Host C4-Binding Protein To Inactivate Complement C4b on the Bacterial Surface
- Source :
- Infection and Immunity. 87
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- Complement is a critical component of antimicrobial immunity. Various complement regulatory proteins prevent host cells from being attacked. Many pathogens have acquired the ability to sequester complement regulators from host plasma to evade complement attack. We describe here how Streptococcus pneumoniae adopts a strategy to prevent the formation of the C3 convertase C4bC2a by the rapid conversion of surface bound C4b and iC4b into C4dg, which remains bound to the bacterial surface but no longer forms a convertase complex. Noncapsular virulence factors on the pneumococcus are thought to facilitate this process by sequestering C4b-binding protein (C4BP) from host plasma. When S. pneumoniae D39 was opsonized with human serum, the larger C4 activation products C4b and iC4b were undetectable, but the bacteria were liberally decorated with C4dg and C4BP. With targeted deletions of either PspA or PspC, C4BP deposition was markedly reduced, and there was a corresponding reduction in C4dg and an increase in the deposition of C4b and iC4b. The effect was greatest when PspA and PspC were both knocked out. Infection experiments in mice indicated that the deletion of PspA and/or PspC resulted in the loss of bacterial pathogenicity. Recombinant PspA and PspC both bound serum C4BP, and both led to increased C4b and reduced C4dg deposition on S. pneumoniae D39. We conclude that PspA and PspC help the pneumococcus to evade complement attack by binding C4BP and so inactivating C4b.
- Subjects :
- 0301 basic medicine
030106 microbiology
Immunology
Virulence
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
Microbiology
Pneumococcal Infections
law.invention
Mice
03 medical and health sciences
Bacterial Proteins
law
Streptococcus pneumoniae
Complement C4b
medicine
Animals
Humans
Opsonin
Immune Evasion
Host Response and Inflammation
C4b-binding protein
Complement C4b-Binding Protein
Binding protein
C3-convertase
Disease Models, Animal
030104 developmental biology
Infectious Diseases
Recombinant DNA
Parasitology
Protein Binding
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....2fbb0ea923d7049c9df7cbdaa20544c4