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Home / Equine Research Bank / Sci Rep / Identification of LukPQ, a novel, equid-adapted leukocidin o...
Scientific reports2017; 7; 40660; doi: 10.1038/srep40660

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.
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Publication Date: 2017-01-20 PubMed ID: 28106142PubMed Central: PMC5247767DOI: 10.1038/srep40660Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article describes the identification and characterization of LukPQ, a new toxin produced by the bacterium Staphylococcus aureus that specifically targets equine (horse) white blood cells. Unlike previously known toxins of this type, LukPQ is shown to be influenced by both components of the toxin, not just the component that binds to the host cell.

Leukocidins and Staphylococcus aureus

  • The study is based on Staphylococcus aureus, a bacterium that secretes toxins known as leukocidins.
  • These toxins target white blood cells, and are composed of two parts: an S-component that binds to a receptor on the host cell, and an F-component that contributes to forming the pore through which the toxins infiltrate the host cell.

Discovery of LukPQ

  • The researchers discovered a new leukocidin, which they named LukPQ. It stands out because its S-component, LukP, is highly similar to another leukocidin (LukED), but the two differ in their species specificity.
  • This leukocidin is encoded on a specific segment of the bacteria’s DNA (ΦSaeq1).
  • It was observed mostly in strains cultured from equine (horse) sources, indicating its specific adaptation for equine hosts.

Impact on equine neutrophils and receptors

  • LukPQ was found to be a potent killer of equine neutrophils, a type of white blood cell involved in immune response.
  • It targets equine-CXCRA and CXCR2 receptors on these cells, helping to establish its equine specificity.

Challenging the existing paradigm

  • Traditionally, the specificity of leukocidins like these was thought to be driven solely by their S-component. However, this study found that the F-component also plays a role in LukPQ’s host tropism (preference for a certain host).
  • The researchers made these findings by forming non-traditional, or “non-canonical,” toxin pairs, which helped them study the role of the F-component.

Cite This Article

APA
Koop G, Vrieling M, Storisteanu DM, Lok LS, Monie T, van Wigcheren G, Raisen C, Ba X, Gleadall N, Hadjirin N, Timmerman AJ, Wagenaar JA, Klunder HM, Fitzgerald JR, Zadoks R, Paterson GK, Torres C, Waller AS, Loeffler A, Loncaric I, Hoet AE, Bergström K, De Martino L, Pomba C, de Lencastre H, Ben Slama K, Gharsa H, Richardson EJ, Chilvers ER, de Haas C, van Kessel K, van Strijp JA, Harrison EM, Holmes MA. (2017). Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus. Sci Rep, 7, 40660. https://doi.org/10.1038/srep40660

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 7
Pages: 40660

Researcher Affiliations

Koop, Gerrit
  • Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
Vrieling, Manouk
  • Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Storisteanu, Daniel M L
  • Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
Lok, Laurence S C
  • Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
Monie, Tom
  • 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.
van Wigcheren, Glenn
  • Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Raisen, Claire
  • Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Ba, Xiaoliang
  • Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Gleadall, Nicholas
  • Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Hadjirin, Nazreen
  • Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
Timmerman, Arjen J
  • Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
Wagenaar, Jaap A
  • 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.
Klunder, Heleen M
  • Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.
Fitzgerald, J Ross
  • The Roslin Institute, University of Edinburgh, EH25 9RG, Edinburgh, United Kingdom.
Zadoks, Ruth
  • 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.
Paterson, Gavin K
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, United Kingdom.
Torres, Carmen
  • Área Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, Logroño 26006, Spain.
Waller, Andrew S
  • Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom.
Loeffler, Anette
  • Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, Hatfield, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
Loncaric, Igor
  • Institute of Microbiology, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
Hoet, Armando E
  • 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.
Bergström, Karin
  • Department of Animal Health and Antimicrobial Strategies, SVA, SE-751 89 Uppsala, Sweden.
De Martino, Luisa
  • Department of Veterinary Medicine and Animal Production, Infectious Diseases Section, University of Naples "Federico II", 80137 Naples, Italy.
Pomba, Constança
  • Interdisciplinary Centre of Research in Animal Health, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 LISBOA, Portugal.
de Lencastre, Hermínia
  • 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.
Ben Slama, Karim
  • 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.
Gharsa, Haythem
  • Laboratoire de Microorganismes et Biomolécules actives, Département de Biologie, Faculté de Sciences de Tunis, 2092 Tunis, Tunisia.
Richardson, Emily J
  • Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK.
Chilvers, Edwin R
  • Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Hills Road, Cambridge CB2 0QQ, United Kingdom.
de Haas, Carla
  • Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
van Kessel, Kok
  • Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
van Strijp, Jos A G
  • Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Harrison, Ewan M
  • Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Holmes, Mark A
  • Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom.

MeSH Terms

  • Animals
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Cattle
  • Cell Survival
  • Gene Order
  • Horse Diseases / microbiology
  • Horses
  • Host Specificity
  • Humans
  • Leukocidins / genetics
  • Leukocidins / metabolism
  • Neutrophils / metabolism
  • Phylogeny
  • Protein Binding
  • Receptors, Interleukin-8B / metabolism
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism

Grant Funding

  • HICF-T5-342 / Department of Health
  • G1001787 / Medical Research Council
  • WT098600 / Wellcome Trust
  • BB/I013873/1 / Biotechnology and Biological Sciences Research Council
  • BB/K00638X/1 / Biotechnology and Biological Sciences Research Council
  • MC_U105960399 / Medical Research Council
  • Wellcome Trust
  • MR/P007201/1 / Medical Research Council
  • MR/N002660/1 / Medical Research Council

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