LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis

Manouk Vrieling*, Eveline M. Boerhout, Glenn F. Van Wigcheren, Kirsten J. Koymans, Tanja G. Mols-Vorstermans, Carla J.C. de Haas, Piet C. Aerts, Ineke J.J.M. Daemen, Kok P.M. Van Kessel, Ad P. Koets, Victor P.M.G. Rutten, Piet J.M. Nuijten, Jos A.G. van Strijp, Lindert Benedictus

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

Abstract

Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in cattle.

Original languageEnglish
Article number37759
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016

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Leukocidins
Bovine Mastitis
Staphylococcus aureus
Mastitis
Neutrophils
Hemolysin Proteins
Virulence Factors
Milk

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Vrieling, M., Boerhout, E. M., Van Wigcheren, G. F., Koymans, K. J., Mols-Vorstermans, T. G., de Haas, C. J. C., ... Benedictus, L. (2016). LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis. Scientific Reports, 6, [37759]. https://doi.org/10.1038/srep37759
Vrieling, Manouk ; Boerhout, Eveline M. ; Van Wigcheren, Glenn F. ; Koymans, Kirsten J. ; Mols-Vorstermans, Tanja G. ; de Haas, Carla J.C. ; Aerts, Piet C. ; Daemen, Ineke J.J.M. ; Van Kessel, Kok P.M. ; Koets, Ad P. ; Rutten, Victor P.M.G. ; Nuijten, Piet J.M. ; van Strijp, Jos A.G. ; Benedictus, Lindert. / LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis. In: Scientific Reports. 2016 ; Vol. 6.
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title = "LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis",
abstract = "Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in cattle.",
author = "Manouk Vrieling and Boerhout, {Eveline M.} and {Van Wigcheren}, {Glenn F.} and Koymans, {Kirsten J.} and Mols-Vorstermans, {Tanja G.} and {de Haas}, {Carla J.C.} and Aerts, {Piet C.} and Daemen, {Ineke J.J.M.} and {Van Kessel}, {Kok P.M.} and Koets, {Ad P.} and Rutten, {Victor P.M.G.} and Nuijten, {Piet J.M.} and {van Strijp}, {Jos A.G.} and Lindert Benedictus",
year = "2016",
doi = "10.1038/srep37759",
language = "English",
volume = "6",
journal = "Scientific Reports",
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Vrieling, M, Boerhout, EM, Van Wigcheren, GF, Koymans, KJ, Mols-Vorstermans, TG, de Haas, CJC, Aerts, PC, Daemen, IJJM, Van Kessel, KPM, Koets, AP, Rutten, VPMG, Nuijten, PJM, van Strijp, JAG & Benedictus, L 2016, 'LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis', Scientific Reports, vol. 6, 37759. https://doi.org/10.1038/srep37759

LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis. / Vrieling, Manouk; Boerhout, Eveline M.; Van Wigcheren, Glenn F.; Koymans, Kirsten J.; Mols-Vorstermans, Tanja G.; de Haas, Carla J.C.; Aerts, Piet C.; Daemen, Ineke J.J.M.; Van Kessel, Kok P.M.; Koets, Ad P.; Rutten, Victor P.M.G.; Nuijten, Piet J.M.; van Strijp, Jos A.G.; Benedictus, Lindert.

In: Scientific Reports, Vol. 6, 37759, 2016.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis

AU - Vrieling, Manouk

AU - Boerhout, Eveline M.

AU - Van Wigcheren, Glenn F.

AU - Koymans, Kirsten J.

AU - Mols-Vorstermans, Tanja G.

AU - de Haas, Carla J.C.

AU - Aerts, Piet C.

AU - Daemen, Ineke J.J.M.

AU - Van Kessel, Kok P.M.

AU - Koets, Ad P.

AU - Rutten, Victor P.M.G.

AU - Nuijten, Piet J.M.

AU - van Strijp, Jos A.G.

AU - Benedictus, Lindert

PY - 2016

Y1 - 2016

N2 - Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in cattle.

AB - Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF′, was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF′ was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF′ in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF′-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF′ as a virulence factor and support the development of therapeutic approaches targeting LukMF′ to control S. aureus mastitis in cattle.

U2 - 10.1038/srep37759

DO - 10.1038/srep37759

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 37759

ER -

Vrieling M, Boerhout EM, Van Wigcheren GF, Koymans KJ, Mols-Vorstermans TG, de Haas CJC et al. LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis. Scientific Reports. 2016;6. 37759. https://doi.org/10.1038/srep37759