Imperial College London
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DrAlexMcCarthy

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3868a.mccarthy Website

 
 
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Location

 

5.40BFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{de:2017:10.1073/pnas.1707032114,
author = {de, Jong NWM and Ramyar, KX and Guerra, FE and Nijland, R and Fevre, C and Voyich, JM and McCarthy, AJ and Garcia, BL and van, Kessel KPM and van, Strijp JAG and Geisbrecht, BV and Haas, P-JA},
doi = {10.1073/pnas.1707032114},
journal = {Proceedings of the National Academy of Sciences},
pages = {9439--9444},
title = {Immune evasion by a staphylococcal inhibitor of myeloperoxidase},
url = {http://dx.doi.org/10.1073/pnas.1707032114},
volume = {114},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein “staphylococcal peroxidase inhibitor” (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-Å resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing.
AU  - de,Jong NWM
AU  - Ramyar,KX
AU  - Guerra,FE
AU  - Nijland,R
AU  - Fevre,C
AU  - Voyich,JM
AU  - McCarthy,AJ
AU  - Garcia,BL
AU  - van,Kessel KPM
AU  - van,Strijp JAG
AU  - Geisbrecht,BV
AU  - Haas,P-JA
DO  - 10.1073/pnas.1707032114
EP  - 9444
PY  - 2017///
SN  - 0027-8424
SP  - 9439
TI  - Immune evasion by a staphylococcal inhibitor of myeloperoxidase
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.1707032114
UR  - https://www.pnas.org/content/114/35/9439
VL  - 114
ER  -
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