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.

Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus / Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel M. L.; Lok, Laurence S. C.; Monie, Tom; Van Wigcheren, Glenn; Raisen, Claire; Ba, Xiaoliang; Gleadall, Nicholas; Hadjirin, Nazreen; Timmerman, Arjen J.; Wagenaar, Jaap A.; Klunder, Heleen M.; Fitzgerald, J. Ross; Zadoks, Ruth; Paterson, Gavin K.; Torres, Carmen; Waller, Andrew S.; Loeffler, Anette; Loncaric, Igor; Hoet, Armando E.; Bergström, Karin; DE MARTINO, Luisa; Pomba, Constança; De Lencastre, Hermínia; Ben Slama, Karim; Gharsa, Haythem; Richardson, Emily J.; Chilvers, Edwin R.; De Haas, Carla; Van Kessel, Kok; Van Strijp, Jos A. G.; Harrison, Ewan M.; Holmes, Mark A.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:(2017), p. 40660. [10.1038/srep40660]

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

DE MARTINO, LUISA;
2017

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.
2017
Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus / Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel M. L.; Lok, Laurence S. C.; Monie, Tom; Van Wigcheren, Glenn; Raisen, Claire; Ba, Xiaoliang; Gleadall, Nicholas; Hadjirin, Nazreen; Timmerman, Arjen J.; Wagenaar, Jaap A.; Klunder, Heleen M.; Fitzgerald, J. Ross; Zadoks, Ruth; Paterson, Gavin K.; Torres, Carmen; Waller, Andrew S.; Loeffler, Anette; Loncaric, Igor; Hoet, Armando E.; Bergström, Karin; DE MARTINO, Luisa; Pomba, Constança; De Lencastre, Hermínia; Ben Slama, Karim; Gharsa, Haythem; Richardson, Emily J.; Chilvers, Edwin R.; De Haas, Carla; Van Kessel, Kok; Van Strijp, Jos A. G.; Harrison, Ewan M.; Holmes, Mark A.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:(2017), p. 40660. [10.1038/srep40660]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/663629
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