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 Loncaric & 14 others Armando 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

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 - 20 Jan 2017

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

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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
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. / 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 Timmerman, {Arjen J.} and Wagenaar, {Jaap A.} and Klunder, {Heleen M.} and Fitzgerald, {J. Ross} and Ruth Zadoks and Paterson, {Gavin K.} and Carmen Torres and Waller, {Andrew S.} and Anette Loeffler and Igor Loncaric and Hoet, {Armando E.} and Karin Bergstr{\"o}m and {De Martino}, Luisa and Constan{\cc}a Pomba and {De Lencastre}, Herm{\'i}nia and {Ben Slama}, Karim and Haythem Gharsa and Richardson, {Emily J.} and Chilvers, {Edwin R.} and {De Haas}, Carla and {Van Kessel}, Kok and {Van Strijp}, {Jos A.G.} and Harrison, {Ewan M.} and Holmes, {Mark 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, Timmerman, AJ, Wagenaar, JA, Klunder, HM, Fitzgerald, JR, Zadoks, R, Paterson, GK, Torres, C, Waller, AS, Loeffler, A, Loncaric, I, Hoet, AE, Bergström, 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 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; 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, Vol. 7, 40660, 20.01.2017.

Research output: Contribution to journalArticle

TY - JOUR

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 - Timmerman, Arjen J.

AU - Wagenaar, Jaap A.

AU - Klunder, Heleen M.

AU - Fitzgerald, J. Ross

AU - Zadoks, Ruth

AU - Paterson, Gavin K.

AU - Torres, Carmen

AU - Waller, Andrew S.

AU - Loeffler, Anette

AU - Loncaric, Igor

AU - Hoet, Armando E.

AU - Bergström, Karin

AU - De Martino, Luisa

AU - Pomba, Constança

AU - De Lencastre, Hermínia

AU - Ben Slama, Karim

AU - Gharsa, Haythem

AU - Richardson, Emily J.

AU - Chilvers, Edwin R.

AU - De Haas, Carla

AU - Van Kessel, Kok

AU - Van Strijp, Jos A.G.

AU - Harrison, Ewan M.

AU - Holmes, Mark A.

PY - 2017/1/20

Y1 - 2017/1/20

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.

UR - http://www.scopus.com/inward/record.url?scp=85010041795&partnerID=8YFLogxK

U2 - 10.1038/srep40660

DO - 10.1038/srep40660

M3 - Article

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 Jan 20;7. 40660. https://doi.org/10.1038/srep40660