Staphylococcus aureus Surface Protein SdrE Binds Complement Regulator Factor H as an Immune Evasion Tactic
Open Access
- 31 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5), e38407
- https://doi.org/10.1371/journal.pone.0038407
Abstract
Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to inhibit the alternative pathway of complement. Here, we report the identification of the surface-associated protein SdrE as a fH-binding protein using purified fH overlay of S. aureus fractionated cell wall proteins and fH cross-linking to S. aureus followed by mass spectrometry. Studies using recombinant SdrE revealed that rSdrE bound significant fH whether from serum or as a purified form, in both a time- and dose-dependent manner. Furthermore, rSdrE-bound fH exhibited cofactor functionality for factor I (fI)-mediated cleavage of C3b to iC3b which correlated positively with increasing amounts of fH. Expression of SdrE on the surface of the surrogate bacterium Lactococcus lactis enhanced recruitment of fH which resulted in increased iC3b generation. Moreover, surface expression of SdrE led to a reduction in C3-fragment deposition, less C5a generation, and reduced killing by polymorphonuclear cells. Thus, we report the first identification of a S. aureus protein associated with the staphylococcal surface that binds factor H as an immune evasion mechanism.Keywords
This publication has 43 references indexed in Scilit:
- Disruption of the alternative pathway convertase occurs at the staphylococcal surface via the acquisition of factor H by Staphylococcus aureusMolecular Immunology, 2011
- Allosteric inhibition of complement function by a staphylococcal immune evasion proteinProceedings of the National Academy of Sciences, 2010
- Complement: a key system for immune surveillance and homeostasisNature Immunology, 2010
- Complement control protein factor H: The good, the bad, and the inadequateMolecular Immunology, 2010
- Characterization of transcription within sdr region of Staphylococcus aureusAntonie van Leeuwenhoek, 2010
- Functional basis for complement evasion by staphylococcal superantigen-like 7Cellular Microbiology, 2010
- Convertase Inhibitory Properties of Staphylococcal Extracellular Complement-binding ProteinJournal of Biological Chemistry, 2010
- Complexity of complement activation in sepsisJournal of Cellular and Molecular Medicine, 2008
- Translational Mini-Review Series on Complement Factor H: Genetics and disease associations of human complement factor HClinical and Experimental Immunology, 2007
- Staphylococcal complement evasion by various convertase-blocking moleculesThe Journal of Experimental Medicine, 2007