Imperial College London

DrDaphneStapels

Faculty of MedicineDepartment of Medicine

Honorary Research Associate
 
 
 
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Contact

 

d.stapels

 
 
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Location

 

Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Woehl:2014:10.4049/jimmunol.1401600,
author = {Woehl, JL and Stapels, DAC and Garcia, BL and Ramyar, KX and Keightley, A and Ruyken, M and Syriga, M and Sfyroera, G and Weber, AB and Zolkiewski, M and Ricklin, D and Lambris, JD and Rooijakkers, SHM and Geisbrecht, BV},
doi = {10.4049/jimmunol.1401600},
journal = {J Immunol},
pages = {6161--6171},
title = {The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase.},
url = {http://dx.doi.org/10.4049/jimmunol.1401600},
volume = {193},
year = {2014}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The pathogenic bacterium Staphylococcus aureus actively evades many aspects of human innate immunity by expressing a series of small inhibitory proteins. A number of these proteins inhibit the complement system, which labels bacteria for phagocytosis and generates inflammatory chemoattractants. Although the majority of staphylococcal complement inhibitors act on the alternative pathway to block the amplification loop, only a few proteins act on the initial recognition cascades that constitute the classical pathway (CP) and lectin pathway (LP). We screened a collection of recombinant, secreted staphylococcal proteins to determine whether S. aureus produces other molecules that inhibit the CP and/or LP. Using this approach, we identified the extracellular adherence protein (Eap) as a potent, specific inhibitor of both the CP and LP. We found that Eap blocked CP/LP-dependent activation of C3, but not C4, and that Eap likewise inhibited deposition of C3b on the surface of S. aureus cells. In turn, this significantly diminished the extent of S. aureus opsonophagocytosis and killing by neutrophils. This combination of functional properties suggested that Eap acts specifically at the level of the CP/LP C3 convertase (C4b2a). Indeed, we demonstrated a direct, nanomolar-affinity interaction of Eap with C4b. Eap binding to C4b inhibited binding of both full-length C2 and its C2b fragment, which indicated that Eap disrupts formation of the CP/LP C3 proconvertase (C4b2). As a whole, our results demonstrate that S. aureus inhibits two initiation routes of complement by expression of the Eap protein, and thereby define a novel mechanism of immune evasion.
AU - Woehl,JL
AU - Stapels,DAC
AU - Garcia,BL
AU - Ramyar,KX
AU - Keightley,A
AU - Ruyken,M
AU - Syriga,M
AU - Sfyroera,G
AU - Weber,AB
AU - Zolkiewski,M
AU - Ricklin,D
AU - Lambris,JD
AU - Rooijakkers,SHM
AU - Geisbrecht,BV
DO - 10.4049/jimmunol.1401600
EP - 6171
PY - 2014///
SP - 6161
TI - The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase.
T2 - J Immunol
UR - http://dx.doi.org/10.4049/jimmunol.1401600
UR - https://www.ncbi.nlm.nih.gov/pubmed/25381436
VL - 193
ER -