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{Stapels:2014:10.1073/pnas.1407616111,
author = {Stapels, DAC and Ramyar, KX and Bischoff, M and von, Köckritz-Blickwede M and Milder, FJ and Ruyken, M and Eisenbeis, J and McWhorter, WJ and Herrmann, M and van, Kessel KPM and Geisbrecht, BV and Rooijakkers, SHM},
doi = {10.1073/pnas.1407616111},
journal = {Proc Natl Acad Sci U S A},
pages = {13187--13192},
title = {Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors.},
url = {http://dx.doi.org/10.1073/pnas.1407616111},
volume = {111},
year = {2014}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Neutrophils are indispensable for clearing infections with the prominent human pathogen Staphylococcus aureus. Here, we report that S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G. The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range. Eap proteins are together essential for NSP inhibition by S. aureus in vitro and promote staphylococcal infection in vivo. The crystal structure of the EapH1/NE complex showed that Eap molecules constitute a unique class of noncovalent protease inhibitors that occlude the catalytic cleft of NSPs. These findings increase our insights into the complex pathogenesis of S. aureus infections and create opportunities to design novel treatment strategies for inflammatory conditions related to excessive NSP activity.
AU - Stapels,DAC
AU - Ramyar,KX
AU - Bischoff,M
AU - von,Köckritz-Blickwede M
AU - Milder,FJ
AU - Ruyken,M
AU - Eisenbeis,J
AU - McWhorter,WJ
AU - Herrmann,M
AU - van,Kessel KPM
AU - Geisbrecht,BV
AU - Rooijakkers,SHM
DO - 10.1073/pnas.1407616111
EP - 13192
PY - 2014///
SP - 13187
TI - Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors.
T2 - Proc Natl Acad Sci U S A
UR - http://dx.doi.org/10.1073/pnas.1407616111
UR - https://www.ncbi.nlm.nih.gov/pubmed/25161283
VL - 111
ER -