title: Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.
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 (ΦSaeq1) 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.
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koop
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Manouk
authors.initials: M
authors.lastname: Vrieling
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Daniel M L
authors.initials: DM
authors.lastname: Storisteanu
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Laurence S C
authors.initials: LS
authors.lastname: Lok
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, United Kingdom.|Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Monie
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Glenn
authors.initials: G
authors.lastname: van Wigcheren
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Raisen
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Ba
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gleadall
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Nazreen
authors.initials: N
authors.lastname: Hadjirin
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
authors.forename: Arjen J
authors.initials: AJ
authors.lastname: Timmerman
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.|Central Veterinary Institute of Wageningen UR, 8200 AB Lelystad, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Wagenaar
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
authors.forename: Heleen M
authors.initials: HM
authors.lastname: Klunder
authors.affiliation: The Roslin Institute, University of Edinburgh, EH25 9RG, Edinburgh, United Kingdom.
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
authors.affiliation: Moredun Research Institute, Bush Loan, Penicuik EH26 0PZ, United Kingdom.|Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Zadoks
authors.affiliation: Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, United Kingdom.
authors.forename: Gavin K
authors.initials: GK
authors.lastname: Paterson
authors.affiliation: Área Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, Logroño 26006, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Torres
authors.affiliation: Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Waller
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
authors.forename: Anette
authors.initials: A
authors.lastname: Loeffler
authors.affiliation: Institute of Microbiology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Loncaric
authors.affiliation: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.|Veterinary Public Health Program, College of Public Health, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
authors.forename: Armando E
authors.initials: AE
authors.lastname: Hoet
authors.affiliation: Department of Animal Health and Antimicrobial Strategies, SVA, SE-751 89 Uppsala, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Bergström
authors.affiliation: Department of Veterinary Medicine and Animal Production, Infectious Diseases Section, University of Naples "Federico II", 80137 Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Martino
authors.affiliation: Interdisciplinary Centre of Research in Animal Health, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 LISBOA, Portugal.
authors.forename: Constança
authors.initials: C
authors.lastname: Pomba
authors.affiliation: Laboratório de Genética Molecular, Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa (ITQB/UNL), Oeiras, Portugal.|Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, NY10065, USA.
authors.forename: Hermínia
authors.initials: H
authors.lastname: de Lencastre
authors.affiliation: Laboratoire de Microorganismes et Biomolécules actives, Département de Biologie, Faculté de Sciences de Tunis, 2092 Tunis, Tunisia.|Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Université de Tunis El Manar, 2092 Tunis, Tunisia.
authors.forename: Karim
authors.initials: K
authors.lastname: Ben Slama
authors.affiliation: Laboratoire de Microorganismes et Biomolécules actives, Département de Biologie, Faculté de Sciences de Tunis, 2092 Tunis, Tunisia.
authors.forename: Haythem
authors.initials: H
authors.lastname: Gharsa
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Richardson
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chilvers
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Carla
authors.initials: C
authors.lastname: de Haas
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Kok
authors.initials: K
authors.lastname: van Kessel
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Ewan M
authors.initials: EM
authors.lastname: Harrison
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival; D023061:Gene Order; D006734:Horse Diseases / Q000382:microbiology; D006736:Horses; D058507:Host Specificity; D006801:Humans; D007956:Leukocidins / Q000235:genetics* / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D007956:Leukocidins; D023063:Receptors, Interleukin-8B