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.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.|Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Manouk
authors.initials: M
authors.lastname: Vrieling
authors.affiliation: Ruminant Research and Development, MSD Animal Health, Wim de Körverstraat 35, 5830 AA Boxmeer, The Netherlands.
authors.forename: Eveline M
authors.initials: EM
authors.lastname: Boerhout
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: van Wigcheren
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Kirsten J
authors.initials: KJ
authors.lastname: Koymans
authors.affiliation: Ruminant Research and Development, MSD Animal Health, Wim de Körverstraat 35, 5830 AA Boxmeer, The Netherlands.
authors.forename: Tanja G
authors.initials: TG
authors.lastname: Mols-Vorstermans
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Carla J C
authors.initials: CJ
authors.lastname: de Haas
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Piet C
authors.initials: PC
authors.lastname: Aerts
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands.
authors.forename: Ineke J J M
authors.initials: IJ
authors.lastname: Daemen
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Kok P M
authors.initials: KP
authors.lastname: van Kessel
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands.|Department of Bacteriology and Epidemiology, Central Veterinary Institute part of Wageningen UR, Edelhertweg 15, 8219 PH Lelystad, The Netherlands.
authors.forename: Ad P
authors.initials: AP
authors.lastname: Koets
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands.|Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
authors.forename: Victor P M G
authors.initials: VP
authors.lastname: Rutten
authors.affiliation: Ruminant Research and Development, MSD Animal Health, Wim de Körverstraat 35, 5830 AA Boxmeer, The Netherlands.
authors.forename: Piet J M
authors.initials: PJ
authors.lastname: Nuijten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.|Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Lindert
authors.initials: L
authors.lastname: Benedictus
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D007956:Leukocidins / Q000096:biosynthesis / Q000378:metabolism*; D008414:Mastitis, Bovine / Q000378:metabolism* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000662:veterinary; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D007956:Leukocidins