Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1

ABSTRACT Although Staphylococcus aureus is best known for infecting humans, bovine-specific strains are a major cause of mastitis in dairy cattle. The bicomponent leukocidin LukMF′, exclusively harbored by S. aureus of ruminant origin, is a virulence factor associated with bovine infections. In this...

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Autores principales:	M. Vrieling, K. J. Koymans, D. A. C. Heesterbeek, P. C. Aerts, V. P. M. G. Rutten, C. J. C. de Haas, K. P. M. van Kessel, A. P. Koets, R. Nijland, J. A. G. van Strijp
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9e359522f60748388c2da2d3d4e4959c
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spelling	oai:doaj.org-article:9e359522f60748388c2da2d3d4e4959c2021-11-15T15:49:02ZBovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR110.1128/mBio.00335-152150-7511https://doaj.org/article/9e359522f60748388c2da2d3d4e4959c2015-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00335-15https://doaj.org/toc/2150-7511ABSTRACT Although Staphylococcus aureus is best known for infecting humans, bovine-specific strains are a major cause of mastitis in dairy cattle. The bicomponent leukocidin LukMF′, exclusively harbored by S. aureus of ruminant origin, is a virulence factor associated with bovine infections. In this study, the molecular basis of the host specificity of LukMF′ is elucidated by identification of chemokine receptor CCR1 as its target. Bovine neutrophils, the major effector cells in the defense against staphylococci, express significant cell surface levels of CCR1, whereas human neutrophils do not. This causes the particular susceptibility of bovine neutrophils to pore formation induced by LukMF′. Bovine S. aureus strains produce high levels of LukMF′ in vitro. In culture supernatant of the mastitis field isolate S1444, LukMF′ was the most important cytotoxic agent for bovine neutrophils. In a fibrin gel matrix, the effects of the in situ secreted toxins on neutrophils migrating toward S. aureus were visualized. Under these physiological ex vivo conditions, bovine S. aureus S1444 efficiently killed approaching neutrophils at a distance through secretion of LukMF′. Altogether, our findings illustrate the coevolution of pathogen and host, provide new targets for therapeutic and vaccine approaches to treat staphylococcal diseases in the cow, and emphasize the importance of staphylococcal toxins in general. IMPORTANCE This study explains the mechanism of action of LukMF′, a bicomponent toxin found in bovine lineages of S. aureus that is associated with mastitis in cattle. At a molecular level, we describe how LukMF′ can specifically kill bovine neutrophils. Here, we demonstrate the contribution of toxins in the determination of host specificity and contribute to the understanding of mechanisms of coevolution of pathogen and host. Our study provides new targets that can be used in therapeutic and vaccine approaches to treat staphylococcal diseases in the cow. We also demonstrate the importance of toxins in specific elimination of immune cells, which has broader implications, especially in human infections.M. VrielingK. J. KoymansD. A. C. HeesterbeekP. C. AertsV. P. M. G. RuttenC. J. C. de HaasK. P. M. van KesselA. P. KoetsR. NijlandJ. A. G. van StrijpAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 3 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 M. Vrieling K. J. Koymans D. A. C. Heesterbeek P. C. Aerts V. P. M. G. Rutten C. J. C. de Haas K. P. M. van Kessel A. P. Koets R. Nijland J. A. G. van Strijp Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
description	ABSTRACT Although Staphylococcus aureus is best known for infecting humans, bovine-specific strains are a major cause of mastitis in dairy cattle. The bicomponent leukocidin LukMF′, exclusively harbored by S. aureus of ruminant origin, is a virulence factor associated with bovine infections. In this study, the molecular basis of the host specificity of LukMF′ is elucidated by identification of chemokine receptor CCR1 as its target. Bovine neutrophils, the major effector cells in the defense against staphylococci, express significant cell surface levels of CCR1, whereas human neutrophils do not. This causes the particular susceptibility of bovine neutrophils to pore formation induced by LukMF′. Bovine S. aureus strains produce high levels of LukMF′ in vitro. In culture supernatant of the mastitis field isolate S1444, LukMF′ was the most important cytotoxic agent for bovine neutrophils. In a fibrin gel matrix, the effects of the in situ secreted toxins on neutrophils migrating toward S. aureus were visualized. Under these physiological ex vivo conditions, bovine S. aureus S1444 efficiently killed approaching neutrophils at a distance through secretion of LukMF′. Altogether, our findings illustrate the coevolution of pathogen and host, provide new targets for therapeutic and vaccine approaches to treat staphylococcal diseases in the cow, and emphasize the importance of staphylococcal toxins in general. IMPORTANCE This study explains the mechanism of action of LukMF′, a bicomponent toxin found in bovine lineages of S. aureus that is associated with mastitis in cattle. At a molecular level, we describe how LukMF′ can specifically kill bovine neutrophils. Here, we demonstrate the contribution of toxins in the determination of host specificity and contribute to the understanding of mechanisms of coevolution of pathogen and host. Our study provides new targets that can be used in therapeutic and vaccine approaches to treat staphylococcal diseases in the cow. We also demonstrate the importance of toxins in specific elimination of immune cells, which has broader implications, especially in human infections.
format	article
author	M. Vrieling K. J. Koymans D. A. C. Heesterbeek P. C. Aerts V. P. M. G. Rutten C. J. C. de Haas K. P. M. van Kessel A. P. Koets R. Nijland J. A. G. van Strijp
author_facet	M. Vrieling K. J. Koymans D. A. C. Heesterbeek P. C. Aerts V. P. M. G. Rutten C. J. C. de Haas K. P. M. van Kessel A. P. Koets R. Nijland J. A. G. van Strijp
author_sort	M. Vrieling
title	Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
title_short	Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
title_full	Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
title_fullStr	Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
title_full_unstemmed	Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
title_sort	bovine <named-content content-type="genus-species">staphylococcus aureus</named-content> secretes the leukocidin lukmf′ to kill migrating neutrophils through ccr1
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/9e359522f60748388c2da2d3d4e4959c
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Bovine <named-content content-type="genus-species">Staphylococcus aureus</named-content> Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1

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