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

Gerrit Koop, Manouk Vrieling, Daniel M.L. Storisteanu, Laurence S.C. Lok, Tom Monie, Glenn Van Wigcheren, Claire Raisen, Xiaoliang Ba, Nicholas Gleadall, Nazreen Hadjirin, Arjen J. Timmerman, Jaap A. Wagenaar, Heleen M. Klunder, J. Ross Fitzgerald, Ruth Zadoks, Gavin K. Paterson, Carmen Torres, Andrew S. Waller, Anette Loeffler, Igor LoncaricArmando E. Hoet, Karin Bergström, Luisa De Martino, Constança Pomba, Hermínia De Lencastre, Karim Ben Slama, Haythem Gharsa, Emily J. Richardson, Edwin R. Chilvers, Carla De Haas, Kok Van Kessel, Jos A.G. Van Strijp, Ewan M. Harrison, Mark A. Holmes

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (Î ▪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.

Original languageEnglish
Article number40660
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 20 Jan 2017

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    Koop, G., Vrieling, M., Storisteanu, D. M. L., Lok, L. S. C., Monie, T., Van Wigcheren, G., ... Holmes, M. A. (2017). Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. Scientific Reports, 7, [40660]. https://doi.org/10.1038/srep40660