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Sci Rep. 2017 Jan 20;7:40660. doi: 10.1038/srep40660.

Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.

Author information

1
Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
2
Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
3
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
4
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, United Kingdom.
5
Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
6
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
7
Central Veterinary Institute of Wageningen UR, 8200 AB Lelystad, The Netherlands.
8
The Roslin Institute, University of Edinburgh, EH25 9RG, Edinburgh, United Kingdom.
9
Moredun Research Institute, Bush Loan, Penicuik EH26 0PZ, United Kingdom.
10
Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom.
11
Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, United Kingdom.
12
Área Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, Logroño 26006, Spain.
13
Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom.
14
Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
15
Institute of Microbiology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
16
Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
17
Veterinary Public Health Program, College of Public Health, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA.
18
Department of Animal Health and Antimicrobial Strategies, SVA, SE-751 89 Uppsala, Sweden.
19
Department of Veterinary Medicine and Animal Production, Infectious Diseases Section, University of Naples "Federico II", 80137 Naples, Italy.
20
Interdisciplinary Centre of Research in Animal Health, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 LISBOA, Portugal.
21
Laboratório de Genética Molecular, Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa (ITQB/UNL), Oeiras, Portugal.
22
Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, NY10065, USA.
23
Laboratoire de Microorganismes et Biomolécules actives, Département de Biologie, Faculté de Sciences de Tunis, 2092 Tunis, Tunisia.
24
Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Université de Tunis El Manar, 2092 Tunis, Tunisia.
25
Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK.
26
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

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.

PMID:
28106142
PMCID:
PMC5247767
DOI:
10.1038/srep40660
[Indexed for MEDLINE]
Free PMC Article

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