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, Jaap A. Wagenaar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 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 - 2017

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Leukocidins
Staphylococcus aureus
Horses
Viral Tropism
Prophages
Species Specificity
Lipid Bilayers
Neutrophils
Leukocytes

Cite this

Koop, G., Vrieling, M., Storisteanu, D. M. L., Lok, L. S. C., Monie, T., Van Wigcheren, G., ... Wagenaar, J. A. (2017). Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. Scientific Reports, 7, [40660]. https://doi.org/10.1038/srep40660
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 ; Wagenaar, Jaap A. / Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. In: Scientific Reports. 2017 ; Vol. 7.
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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 Wagenaar, {Jaap A.}",
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Koop, G, Vrieling, M, Storisteanu, DML, Lok, LSC, Monie, T, Van Wigcheren, G, Raisen, C, Ba, X, Gleadall, N, Hadjirin, N & Wagenaar, JA 2017, 'Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus', Scientific Reports, vol. 7, 40660. https://doi.org/10.1038/srep40660

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; Wagenaar, Jaap A.

In: Scientific Reports, Vol. 7, 40660, 2017.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus

AU - Koop, Gerrit

AU - Vrieling, Manouk

AU - Storisteanu, Daniel M.L.

AU - Lok, Laurence S.C.

AU - Monie, Tom

AU - Van Wigcheren, Glenn

AU - Raisen, Claire

AU - Ba, Xiaoliang

AU - Gleadall, Nicholas

AU - Hadjirin, Nazreen

AU - Wagenaar, Jaap A.

PY - 2017

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N2 - 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.

AB - 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.

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DO - 10.1038/srep40660

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VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 40660

ER -

Koop G, Vrieling M, Storisteanu DML, Lok LSC, Monie T, Van Wigcheren G et al. Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. Scientific Reports. 2017;7. 40660. https://doi.org/10.1038/srep40660