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 journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)40660
JournalScientific Reports
Volume7
Early online date20 Jan 2017
DOIs
Publication statusE-pub ahead of print - 20 Jan 2017

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