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Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus

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Title: Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus
Authors: Koop, G
Vrieling, M
Storisteanu, DML
Lok, LSC
Monie, T
Van Wigcheren, G
Raisen, C
Ba, X
Gleadall, N
Hadjirin, N
Timmerman, AJ
Wagenaar, JA
Klunder, HM
Fitzgerald, JR
Zadoks, R
Paterson, GK
Torres, C
Waller, AS
Loeffler, A
Loncaric, I
Hoet, AE
Bergstrom, K
De Martino, L
Pomba, C
De Lencastre, H
Ben Slama, K
Gharsa, H
Richardson, EJ
Chilvers, ER
De Haas, C
Van Kessel, K
Van Strijp, JAG
Harrison, EM
Holmes, MA
Item Type: Journal Article
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 (ΦSaeq1) 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.
Issue Date: 20-Jan-2017
Date of Acceptance: 8-Dec-2016
URI: http://hdl.handle.net/10044/1/64631
DOI: https://dx.doi.org/10.1038/srep40660
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: © 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
PANTON-VALENTINE LEUCOCIDIN
HUMAN C5A RECEPTORS
GAMMA-HEMOLYSIN
CHEMOKINE RECEPTORS
HORSES
PROTEIN
LEUKOTOXIN
BINDING
BOVINE
LYMPHOCYTES
Animals
Bacterial Toxins
Cattle
Cell Survival
Gene Order
Horse Diseases
Horses
Host Specificity
Humans
Leukocidins
Neutrophils
Phylogeny
Protein Binding
Receptors, Interleukin-8B
Staphylococcal Infections
Staphylococcus aureus
Publication Status: Published
Article Number: 40660
Online Publication Date: 2017-01-20
Appears in Collections:National Heart and Lung Institute