@article{e8de02566c564d14865c781a08a392b8,
title = "Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus",
abstract = "Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage ({\^I} ▪Saeq1) found in six different clonal lineages, almost exclusively in strains cultured from equids. We show that LukPQ is a potent and specific killer of equine neutrophils and identify equine-CXCRA and CXCR2 as its target receptors. Although the S-component (LukP) is highly similar to the S-component of LukED, the species specificity of LukPQ and LukED differs. By forming non-canonical toxin pairs, we identify that the F-component contributes to the observed host tropism of LukPQ, thereby challenging the current paradigm that leukocidin specificity is driven solely by the S-component.",
author = "Gerrit Koop and Manouk Vrieling and Storisteanu, {Daniel M L} and Lok, {Laurence S C} and Tom Monie and {Van Wigcheren}, Glenn and Claire Raisen and Xiaoliang Ba and Nicholas Gleadall and Nazreen Hadjirin and Timmerman, {Arjen J.} and Wagenaar, {Jaap A.} and Klunder, {Heleen M.} and Fitzgerald, {J. Ross} and Ruth Zadoks and Paterson, {Gavin K.} and Carmen Torres and Waller, {Andrew S.} and Anette Loeffler and Igor Loncaric and Hoet, {Armando E.} and Karin Bergstr{\"o}m and {De Martino}, Luisa and Constan{\c c}a Pomba and {De Lencastre}, Herm{\'i}nia and {Ben Slama}, Karim and Haythem Gharsa and Richardson, {Emily J.} and Chilvers, {Edwin R.} and {Gosselaar-de Haas}, CJC and {van Kessel}, CPM and {Van Strijp}, {Jos A G} and Harrison, {Ewan M.} and Holmes, {Mark A.}",
note = "Funding Information: This work was supported by a Medical Research Council Partnership Grant (G1001787/1) held at the University of Cambridge (MAH, RNZ). GK acknowledges the receipt of a fellowship from the OECD Co-operative Research Programme: Biological Resource Management for Sustainable Agricultural Systems in 2014. MV was supported by the ALTANT project of the Ministry of Economic Affairs of the Dutch Government. JRF was supported by a project grant (BB/K00638X/1) and institute strategic grant funding (ISP3) from the Biotechnology and Biological Sciences Research Council (UK). LSCL is a Wellcome Trust Research Training Fellow and DMLS is a Cambridge Gates Scholar; the work by LSCL, MNLS and ERC was funded in part by the NIHR Cambridge BRC. EMH's position was funded by Health Innovation Challenge Fund, WT098600, HICF-T5-342. This publication presents independent research supported by the Health Innovation Challenge Fund (WT098600, HICF-T5-342), a parallel funding partnership between the Department of Health and Wellcome Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health or Wellcome Trust. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
month = jan,
day = "20",
doi = "10.1038/srep40660",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}