FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2017-01-20 PubMed ID: 28106142PubMed Central: PMC5247767DOI: 10.1038/srep40660Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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

References

This article includes 56 references
  1. Viana D. Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI-carried variants of von Willebrand factor-binding protein. Mol. Microbiol. 77, 1583–1594 (2010).
    pubmed: 20860091
  2. Guinane C M. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biol. Evol. 2, 454–466 (2010).
    pmc: PMC2997551pubmed: 20624747
  3. Viana D. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nat. Genet. 47, 361–366 (2015).
    pmc: PMC4824278pubmed: 25685890
  4. Alonzo F III, Torres V J. The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol. Mol. Biol. Rev. 78, 199–230 (2014).
    pmc: PMC4054254pubmed: 24847020
  5. McCarthy A J, Lindsay J A. Staphylococcus aureus innate immune evasion is lineage-specific: A bioinfomatics study. Infect. Genet. Evol. 19, 7–14 (2013).
    pubmed: 23792184
  6. Yamada T. Leukotoxin family genes in Staphylococcus aureus isolated from domestic animals and prevalence of lukM-lukF-PV genes by bacteriophages in bovine isolates. Vet. Microbiol. 110, 97–103 (2005).
    pubmed: 16112825
  7. Herron-Olson L, Fitzgerald J R, Musser J M, Kapur V. Molecular correlates of host specialization in Staphylococcus aureus. PLoS ONE 2 (2007).
    pmc: PMC2040198pubmed: 17971880
  8. Schlotter K. Leukocidin genes lukF-P83 and lukM are associated with Staphylococcus aureus clonal complexes 151, 479 and 133 isolated from bovine udder infections in Thuringia, Germany. Vet. Res. 43 (2012).
    pmc: PMC3416645pubmed: 22587484
  9. Spaan A N. The staphylococcal toxin Panton-Valentine Leukocidin targets human C5a receptors. Cell Host Microbe 13, 584–594 (2013).
    pubmed: 23684309
  10. Alonzo F III. CCR5 is a receptor for Staphylococcus aureus leukotoxin ED. Nature 493, 51–55 (2013).
    pmc: PMC3536884pubmed: 23235831
  11. Reyes-Robles T. Staphylococcus aureus Leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to Kill leukocytes and promote infection. Cell Host Microbe 14, 453–459 (2013).
    pmc: PMC3876884pubmed: 24139401
  12. Spaan A N. The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors. Nat. Commun. 5, 5438 (2014).
    pmc: PMC4228697pubmed: 25384670
  13. Löffler B. Staphylococcus aureus Panton-Valentine Leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog. 6 (2010).
    pmc: PMC2798753pubmed: 20072612
  14. Vrieling M. Bovine Staphylococcus aureus secretes the leukocidin LukMF’ to kill migrating neutrophils through CCR1. mBio 6 (2015).
    pmc: PMC4462618pubmed: 26045537
  15. Barrio M B, Rainard P, Prévost G. LukM/LukF′-PV is the most active Staphylococcus aureus leukotoxin on bovine neutrophils. Microbes Infect. 8, 2068–2074 (2006).
    pubmed: 16782383
  16. Boakes E. Distinct bacteriophages encoding panton-valentine leukocidin (PVL) among international methicillin-resistant Staphylococcus aureus clones harboring PVL. J. Clin. Microbiol. 49, 684–692 (2011).
    pmc: PMC3043515pubmed: 21106787
  17. Loncaric I. Identification and characterization of methicillin-resistant Staphylococcus aureus (MRSA) from Austrian companion animals and horses. Vet. Microbiol. 168, 381–387 (2014).
    pubmed: 24332703
  18. Van Balen J. Molecular epidemiology of environmental MRSA at an equine teaching hospital: Introduction, circulation and maintenance. Vet. Res. 45 (2014).
    pmc: PMC3974172pubmed: 24641543
  19. Bergström K, Aspan A, Landén A, Johnston C, Grönlund-Andersson U. The first nosocomial outbreak of methicillin-resistant Staphylococcus aureus in horses in Sweden. Acta Vet. Scand. 54 (2012).
    pmc: PMC3348035pubmed: 22316072
  20. Couto N. Biocide and antimicrobial susceptibility of methicillin-resistant Staphylococcal isolates from horses. Vet. Microbiol. 166, 299–303 (2013).
    pubmed: 23845732
  21. Mallardo K, Nizza S, Fiorito F, Pagnini U, De Martino L. A comparative evaluation of methicillin-resistant staphylococci isolated from harness racing-horses, breeding mares and riding-horses in Italy. Asian Pac. J. Trop. Biomed. 3, 169–173 (2013).
    pmc: PMC3631744pubmed: 23620832
  22. Gómez-Sanz E. First detection of methicillin-resistant Staphylococcus aureus ST398 and Staphylococcus pseudintermedius ST68 from hospitalized equines in Spain. Zoonoses Public Health 61, 192–201 (2014).
    pubmed: 23773775
  23. Abdelbary M M H. Phylogenetic analysis of Staphylococcus aureus CC398 reveals a sub-lineage epidemiologically associated with infections in horses. PLoS ONE 9 (2014).
    pmc: PMC3913741pubmed: 24505386
  24. Rigby K M, DeLeo F R. Neutrophils in innate host defense against Staphylococcus aureus infections. Semin. Immun. 34, 237–259 (2012).
    pmc: PMC3271231pubmed: 22080185
  25. Widdison S. The bovine chemokine receptors and their mRNA abundance in mononuclear phagocytes. BMC Genomics 11 (2010).
    pmc: PMC3091636pubmed: 20642824
  26. Koymans K J, Vrieling M, Gorham R D, van Strijp J A G. In Current Topics in Microbiology and Immunology (ed Compans R. W. et al..) 1–49 (Springer Berlin Heidelberg, Berlin, Heidelberg, 2016). .
  27. Weese J S, van Duijkeren E. Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius in veterinary medicine. Vet. Microbiol. 140, 418–429 (2010).
    pubmed: 19246166
  28. van Duijkeren E. Methicillin-resistant Staphylococcus aureus in horses and horse personnel: An investigation of several outbreaks. Vet. Microbiol. 141, 96–102 (2010).
    pubmed: 19740613
  29. Schwaber M J. Clonal transmission of a rare methicillin-resistant Staphylococcus aureus genotype between horses and staff at a veterinary teaching hospital. Vet. Microbiol. 162, 907–911 (2013).
    pubmed: 23265243
  30. Sieber S. Evolution of multidrug-resistant Staphylococcus aureus infections in horses and colonized personnel in an equine clinic between 2005 and 2010. Microb. Drug Resist. 17, 471–478 (2011).
    pubmed: 21875361
  31. Siwicki A K. In vitro effect of staphylococcal leukocidins (LukE, LukD) on the proliferative responses of blood lymphocytes in dog (Canis familiaris). Bull. Vet. Inst. Pulawy 47, 395–401 (2003).
  32. Bownik A. In vitro effects of staphylococcal leukocidin LukE/LukD on the proliferative ability of lymphocytes isolated from common carp (Cyprinus carpio L.). Fish Shellfish Immunol. 20, 656–659 (2006).
    pubmed: 16183304
  33. Spaan A N. Differential interaction of the staphylococcal toxins Panton-Valentine Leukocidin and γ-hemolysin CB with human C5a receptors. J. Immunol. 195, 1034–1043 (2015).
    pmc: PMC4506853pubmed: 26091719
  34. Brooks A C, Rickards K J, Cunningham F M. CXCL8 attenuates chemoattractant-induced equine neutrophil migration. Vet. Immunol. Immunopathol. 139, 141–147 (2011).
    pubmed: 21040981
  35. Monma N, Nguyen V T, Kaneko J, Higuchi H, Kamio Y. Essential residues, W177 and R198, of LukF for phosphatidylcholine-binding and pore-formation by staphylococcal γ-hemolysin on human erythrocyte membranes. J. Biochem. 136, 427–431 (2004).
    pubmed: 15625310
  36. Meyer F, Girardot R, Piémont Y, Prévost G, Colin D A. Analysis of the specificity of panton-valentine leucocidin and gamma-hemolysin F component binding. Infect. Immun. 77, 266–273 (2009).
    pmc: PMC2612235pubmed: 18838523
  37. Prevost G. Panton-valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect. Immun. 63, 4121–4129 (1995).
    pmc: PMC173579pubmed: 7558328
  38. Yamashita D. Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins. Nat. Commun. 5 (2014).
    pubmed: 25263813
  39. Gharsa H. High diversity of genetic lineages and virulence genes in nasal Staphylococcus aureus isolates from donkeys destined to food consumption in Tunisia with predominance of the ruminant associated CC133 lineage. BMC Vet. Res. 8 (2012).
    pmc: PMC3538696pubmed: 23107174
  40. Aires-de-Sousa M. Characterization of Staphylococcus aureus isolates from buffalo, bovine, ovine, and caprine milk samples collected in Rio de Janeiro State, Brazil. Appl. Environ. Microbiol. 73, 3845–3849 (2007).
    pmc: PMC1932710pubmed: 17449696
  41. Zhou Y, Liang Y, Lynch K H, Dennis J J, Wishart D S. PHAST: A Fast Phage Search Tool. Nucleic Acids Res. 39, W347–W352 (2011).
    pmc: PMC3125810pubmed: 21672955
  42. Bergström K, Bengtsson B, Nyman A, Grönlund Andersson U. Longitudinal study of horses for carriage of methicillin-resistant Staphylococcus aureus following wound infections. Vet. Microbiol. 163, 388–391 (2013).
    pubmed: 23428383
  43. Surewaard B G, van Strijp J A, Nijland R. Studying interactions of Staphylococcus aureus with neutrophils by flow cytometry and time lapse microscopy. J. Vis. Exp. 77 (2013).
    pmc: PMC3814803pubmed: 23893048
  44. Siemsen D W, Schepetkin I A, Kirpotina L N, Lei B, Quinn M T. Neutrophil isolation from nonhuman species. Methods Mol. Biol. 412, 21–34 (2007).
    pubmed: 18453103
  45. Ko Y P. Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface. PLoS Pathog. 9, 1–13 (2013).
    pmc: PMC3861539pubmed: 24348255
  46. Perret M. Cross-talk between Staphylococcus aureus leukocidins-intoxicated macrophages and lung epithelial cells triggers chemokine secretion in an inflammasome-dependent manner. Cell. Microbiol. 14, 1019–1036 (2012).
    pubmed: 22329718
  47. Amatruda T T III, Steele D A, Slepak V Z, Simon M I. Ga16, a G protein a subunit specifically expressed in hematopoietic cells. Proc. Natl. Acad. Sci. USA 88, 5587–5591 (1991).
    pmc: PMC51922pubmed: 1905813
  48. De Haas C J C. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J. Exp. Med. 199, 687–695 (2004).
    pmc: PMC2213298pubmed: 14993252
  49. Shi J, Blundell T L, Mizuguchi K. FUGUE: Sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. J. Mol. Biol. 310, 243–257 (2001).
    pubmed: 11419950
  50. Nocadello S. Crystal structures of the components of the Staphylococcus aureus leukotoxin ED. Acta Crystallograph. Sect. D, Struct. Biol. 72, 113–120 (2015).
    pmc: PMC4756620pubmed: 26894539
  51. Park S H. Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature 491, 779–783 (2012).
    pmc: PMC3700570pubmed: 23086146
  52. Krivov G G, Shapovalov M V, Dunbrack R L Jr. Improved prediction of protein side-chain conformations with SCWRL4. Proteins Struct. Funct. Bioinform. 77, 778–795 (2009).
    pmc: PMC2885146pubmed: 19603484
  53. Chen V B. MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallograph. Sect. D Biolog. Cryst. 66, 12–21 (2010).
    pmc: PMC2803126pubmed: 20057044
  54. Sievers F. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7 (2011).
    pmc: PMC3261699pubmed: 21988835
  55. Dobson L, Langó T, Reményi I, Tusnády G E. Expediting topology data gathering for the TOPDB database. Nucleic Acids Res. 43, D283–D289 (2015).
    pmc: PMC4383934pubmed: 25392424
  56. Dobson L, Reményi I, Tusnády G E. The human transmembrane proteome. Biol. Direct 10 (2015).
    pmc: PMC4445273pubmed: 26018427

Citations

This article has been cited 38 times.
  1. Mlynarczyk-Bonikowska B, Rudnicka L. The Pathogenicity Mechanisms of Staphylococcus aureus. Int J Mol Sci 2025 Dec 6;26(24).
    doi: 10.3390/ijms262411803pubmed: 41465232google scholar: lookup
  2. Jiang W, Chen H, Liu Z, Dang Y, Da Y, Liu Z, Zhu Y, Gao L, Yan W, Han J, You C. Histidinol dehydrogenase (HisD): a critical regulator of Staphylococcus aureus virulence and a promising target for antivirulence therapy. Microbiol Spectr 2026 Jan 6;14(1):e0142925.
    doi: 10.1128/spectrum.01429-25pubmed: 41294339google scholar: lookup
  3. Wolfgramm H, Busch LM, Tebben J, Mehlan H, Hagenau L, Sura T, Hoffmüller T, Bludau E, Gesell Salazar M, Reder A, Michalik S, Steil L, Surmann K, Mäder U, Holtfreter S, Völker U. Integrated genomic and proteomic analysis of the mouse-adapted Staphylococcus aureus strain JSNZ. Curr Res Microb Sci 2025;9:100489.
    doi: 10.1016/j.crmicr.2025.100489pubmed: 41146725google scholar: lookup
  4. Sproch J, Prescott R, Kim HJ, Chaguza C, Gonzalez S, Ilmain JK, Shopsin B, Ratner AJ, Torres VJ. Cell targeting by the bicomponent leukocidin subunit HlgB drives Staphylococcus aureus pathophysiology. J Biol Chem 2025 Oct;301(10):110592.
    doi: 10.1016/j.jbc.2025.110592pubmed: 40812424google scholar: lookup
  5. Müller E, Monecke S, Armengol Porta M, Narvaez Encalada MV, Reissig A, Rüttiger L, Schröttner P, Schwede I, Söffing HH, Thürmer A, Ehricht R. Rapid Detection of Panton-Valentine Leukocidin Production in Clinical Isolates of Staphylococcus aureus from Saxony and Brandenburg and Their Molecular Characterisation. Pathogens 2025 Mar 1;14(3).
    doi: 10.3390/pathogens14030238pubmed: 40137723google scholar: lookup
  6. Monecke S, Burgold-Voigt S, Feßler AT, Krapf M, Loncaric I, Liebler-Tenorio EM, Braun SD, Diezel C, Müller E, Reinicke M, Reissig A, Cabal Rosel A, Ruppitsch W, Hotzel H, Hanke D, Cuny C, Witte W, Schwarz S, Ehricht R. Characterisation of Staphylococcus aureus Strains and Their Prophages That Carry Horse-Specific Leukocidin Genes lukP/Q. Toxins (Basel) 2025 Jan 3;17(1).
    doi: 10.3390/toxins17010020pubmed: 39852974google scholar: lookup
  7. Yebra G, Mrochen D, Fischer S, Pfaff F, Ulrich RG, Pritchett-Corning K, Holtfreter S, Fitzgerald JR. Bacteriophage-driven emergence and expansion of Staphylococcus aureus in rodent populations. PLoS Pathog 2024 Jul;20(7):e1012378.
    doi: 10.1371/journal.ppat.1012378pubmed: 39047021google scholar: lookup
  8. Barber MF, Fitzgerald JR. Mechanisms of host adaptation by bacterial pathogens. FEMS Microbiol Rev 2024 Jun 20;48(4).
    doi: 10.1093/femsre/fuae019pubmed: 39003250google scholar: lookup
  9. Zhu Z, Hu Z, Li S, Fang R, Ono HK, Hu DL. Molecular Characteristics and Pathogenicity of Staphylococcus aureus Exotoxins. Int J Mol Sci 2023 Dec 28;25(1).
    doi: 10.3390/ijms25010395pubmed: 38203566google scholar: lookup
  10. Cheung GYC, Otto M. Virulence Mechanisms of Staphylococcal Animal Pathogens. Int J Mol Sci 2023 Sep 26;24(19).
    doi: 10.3390/ijms241914587pubmed: 37834035google scholar: lookup
  11. Matuszewska M, Dabrowska A, Murray GGR, Kett SM, Vick AJA, Banister SC, Pantoja Munoz L, Cunningham P, Welch JJ, Holmes MA, Weinert LA. Absence of Staphylococcus aureus in Wild Populations of Fish Supports a Spillover Hypothesis. Microbiol Spectr 2023 Aug 17;11(4):e0485822.
    doi: 10.1128/spectrum.04858-22pubmed: 37341608google scholar: lookup
  12. Burgold-Voigt S, Monecke S, Busch A, Bocklisch H, Braun SD, Diezel C, Hotzel H, Liebler-Tenorio EM, Müller E, Reinicke M, Reissig A, Ruppelt-Lorz A, Ehricht R. Characterisation of a Staphylococcus aureus Isolate Carrying Phage-Borne Enterotoxin E from a European Badger (Meles meles). Pathogens 2023 May 12;12(5).
    doi: 10.3390/pathogens12050704pubmed: 37242375google scholar: lookup
  13. Shoaib M, Aqib AI, Muzammil I, Majeed N, Bhutta ZA, Kulyar MF, Fatima M, Zaheer CF, Muneer A, Murtaza M, Kashif M, Shafqat F, Pu W. MRSA compendium of epidemiology, transmission, pathophysiology, treatment, and prevention within one health framework. Front Microbiol 2022;13:1067284.
    doi: 10.3389/fmicb.2022.1067284pubmed: 36704547google scholar: lookup
  14. Chaguza C, Smith JT, Bruce SA, Gibson R, Martin IW, Andam CP. Prophage-encoded immune evasion factors are critical for Staphylococcus aureus host infection, switching, and adaptation. Cell Genom 2022 Nov 9;2(11).
    doi: 10.1016/j.xgen.2022.100194pubmed: 36465278google scholar: lookup
  15. Monecke S, Roberts MC, Braun SD, Diezel C, Müller E, Reinicke M, Linde J, Joshi PR, Paudel S, Acharya M, Chalise MK, Feßler AT, Hotzel H, Khanal L, Koju NP, Schwarz S, Kyes RC, Ehricht R. Sequence Analysis of Novel Staphylococcus aureus Lineages from Wild and Captive Macaques. Int J Mol Sci 2022 Sep 23;23(19).
    doi: 10.3390/ijms231911225pubmed: 36232529google scholar: lookup
  16. Naji Hasan R, Abdal Kareem Jasim S. Detection of Panton-Valentine leukocidin and MecA Genes in Staphylococcus aureus isolated from Iraqi Patients. Arch Razi Inst 2021 Oct;76(4):1054-1059.
    doi: 10.22092/ari.2021.355962.1751pubmed: 35096341google scholar: lookup
  17. Monecke S, Feßler AT, Burgold-Voigt S, Krüger H, Mühldorfer K, Wibbelt G, Liebler-Tenorio EM, Reinicke M, Braun SD, Hanke D, Diezel C, Müller E, Loncaric I, Schwarz S, Ehricht R. Staphylococcus aureus isolates from Eurasian Beavers (Castor fiber) carry a novel phage-borne bicomponent leukocidin related to the Panton-Valentine leukocidin. Sci Rep 2021 Dec 22;11(1):24394.
    doi: 10.1038/s41598-021-03823-6pubmed: 34937862google scholar: lookup
  18. Ben Chehida F, Gharsa H, Tombari W, Selmi R, Khaldi S, Daaloul M, Ben Slama K, Messadi L. First Report of Antimicrobial Susceptibility and Virulence Gene Characterization Associated with Staphylococcus aureus Carriage in Healthy Camels from Tunisia. Animals (Basel) 2021 Sep 21;11(9).
    doi: 10.3390/ani11092754pubmed: 34573722google scholar: lookup
  19. Nhatsave N, Garrine M, Messa A Jr, Massinga AJ, Cossa A, Vaz R, Ombi A, Zimba TF, Alfredo H, Mandomando I, Tchamo C. Molecular Characterization of Staphylococcus aureus Isolated from Raw Milk Samples of Dairy Cows in Manhiça District, Southern Mozambique. Microorganisms 2021 Aug 8;9(8).
    doi: 10.3390/microorganisms9081684pubmed: 34442763google scholar: lookup
  20. Wegener A, Broens EM, van der Graaf-van Bloois L, Zomer AL, Visser CE, van Zeijl J, van der Meer C, Kusters JG, Friedrich AW, Kampinga GA, Sips GJ, Smeets L, van Kerckhoven MEJ, Timmerman AJ, Wagenaar JA, Duim B. Absence of Host-Specific Genes in Canine and Human Staphylococcus pseudintermedius as Inferred from Comparative Genomics. Antibiotics (Basel) 2021 Jul 14;10(7).
    doi: 10.3390/antibiotics10070854pubmed: 34356775google scholar: lookup
  21. Little SV, Hillhouse AE, Lawhon SD, Bryan LK. Analysis of Virulence and Antimicrobial Resistance Gene Carriage in Staphylococcus aureus Infections in Equids Using Whole-Genome Sequencing. mSphere 2021 Aug 25;6(4):e0019620.
    doi: 10.1128/mSphere.00196-20pubmed: 34346711google scholar: lookup
  22. Ruiz-Ripa L, Simón C, Ceballos S, Ortega C, Zarazaga M, Torres C, Gómez-Sanz E. S. pseudintermedius and S. aureus lineages with transmission ability circulate as causative agents of infections in pets for years. BMC Vet Res 2021 Jan 21;17(1):42.
    doi: 10.1186/s12917-020-02726-4pubmed: 33478473google scholar: lookup
  23. Tromp AT, van Strijp JAG. Studying Staphylococcal Leukocidins: A Challenging Endeavor. Front Microbiol 2020;11:611.
    doi: 10.3389/fmicb.2020.00611pubmed: 32351474google scholar: lookup
  24. Mama OM, Gómez P, Ruiz-Ripa L, Gómez-Sanz E, Zarazaga M, Torres C. Antimicrobial Resistance, Virulence, and Genetic Lineages of Staphylococci from Horses Destined for Human Consumption: High Detection of S. aureus Isolates of Lineage ST1640 and Those Carrying the lukPQ Gene. Animals (Basel) 2019 Nov 1;9(11).
    doi: 10.3390/ani9110900pubmed: 31683871google scholar: lookup
  25. Scholtzek AD, Hanke D, Walther B, Eichhorn I, Stöckle SD, Klein KS, Gehlen H, Lübke-Becker A, Schwarz S, Feßler AT. Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility. Toxins (Basel) 2019 Sep 13;11(9).
    doi: 10.3390/toxins11090535pubmed: 31540335google scholar: lookup
  26. Abouelkhair MA, Bemis DA, Giannone RJ, Frank LA, Kania SA. Identification, cloning and characterization of SpEX exotoxin produced by Staphylococcus pseudintermedius. PLoS One 2019;14(7):e0220301.
    doi: 10.1371/journal.pone.0220301pubmed: 31356636google scholar: lookup
  27. Shumba P, Mairpady Shambat S, Siemens N. The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections. Toxins (Basel) 2019 Jun 11;11(6).
    doi: 10.3390/toxins11060332pubmed: 31212697google scholar: lookup
  28. Haag AF, Fitzgerald JR, Penadés JR. Staphylococcus aureus in Animals. Microbiol Spectr 2019 May;7(3).
    doi: 10.1128/microbiolspec.GPP3-0060-2019pubmed: 31124433google scholar: lookup
  29. Tam K, Torres VJ. Staphylococcus aureus Secreted Toxins and Extracellular Enzymes. Microbiol Spectr 2019 Mar;7(2).
    doi: 10.1128/microbiolspec.GPP3-0039-2018pubmed: 30873936google scholar: lookup
  30. Walther B, Klein KS, Barton AK, Semmler T, Huber C, Merle R, Tedin K, Mitrach F, Lübke-Becker A, Gehlen H. Equine Methicillin-Resistant Sequence Type 398 Staphylococcus aureus (MRSA) Harbor Mobile Genetic Elements Promoting Host Adaptation. Front Microbiol 2018;9:2516.
    doi: 10.3389/fmicb.2018.02516pubmed: 30405574google scholar: lookup
  31. Abouelkhair MA, Bemis DA, Giannone RJ, Frank LA, Kania SA. Characterization of a leukocidin identified in Staphylococcus pseudintermedius. PLoS One 2018;13(9):e0204450.
    doi: 10.1371/journal.pone.0204450pubmed: 30261001google scholar: lookup
  32. Mekonnen SA, Lam TJGM, Hoekstra J, Rutten VPMG, Tessema TS, Broens EM, Riesebos AE, Spaninks MP, Koop G. Characterization of Staphylococcus aureus isolated from milk samples of dairy cows in small holder farms of North-Western Ethiopia. BMC Vet Res 2018 Aug 23;14(1):246.
    doi: 10.1186/s12917-018-1558-1pubmed: 30139356google scholar: lookup
  33. He C, Xu S, Zhao H, Hu F, Xu X, Jin S, Yang H, Gong F, Liu Q. Leukotoxin and pyrogenic toxin Superantigen gene backgrounds in bloodstream and wound Staphylococcus aureus isolates from eastern region of China. BMC Infect Dis 2018 Aug 13;18(1):395.
    doi: 10.1186/s12879-018-3297-0pubmed: 30103694google scholar: lookup
  34. Richardson EJ, Bacigalupe R, Harrison EM, Weinert LA, Lycett S, Vrieling M, Robb K, Hoskisson PA, Holden MTG, Feil EJ, Paterson GK, Tong SYC, Shittu A, van Wamel W, Aanensen DM, Parkhill J, Peacock SJ, Corander J, Holmes M, Fitzgerald JR. Gene exchange drives the ecological success of a multi-host bacterial pathogen. Nat Ecol Evol 2018 Sep;2(9):1468-1478.
    doi: 10.1038/s41559-018-0617-0pubmed: 30038246google scholar: lookup
  35. Hoekstra J, Rutten V, Sommeling L, van Werven T, Spaninks M, Duim B, Benedictus L, Koop G. High Production of LukMF' in Staphylococcus aureus Field Strains Is Associated with Clinical Bovine Mastitis. Toxins (Basel) 2018 May 15;10(5).
    doi: 10.3390/toxins10050200pubmed: 29762488google scholar: lookup
  36. Tromp AT, Van Gent M, Abrial P, Martin A, Jansen JP, De Haas CJC, Van Kessel KPM, Bardoel BW, Kruse E, Bourdonnay E, Boettcher M, McManus MT, Day CJ, Jennings MP, Lina G, Vandenesch F, Van Strijp JAG, Lebbink RJ, Haas PA, Henry T, Spaan AN. Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin. Nat Microbiol 2018 Jun;3(6):708-717.
    doi: 10.1038/s41564-018-0159-xpubmed: 29736038google scholar: lookup
  37. de Jong NWM, Vrieling M, Garcia BL, Koop G, Brettmann M, Aerts PC, Ruyken M, van Strijp JAG, Holmes M, Harrison EM, Geisbrecht BV, Rooijakkers SHM. Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains. J Biol Chem 2018 Mar 23;293(12):4468-4477.
    doi: 10.1074/jbc.RA117.000599pubmed: 29414776google scholar: lookup
  38. Spaan AN, van Strijp JAG, Torres VJ. Leukocidins: staphylococcal bi-component pore-forming toxins find their receptors. Nat Rev Microbiol 2017 Jul;15(7):435-447.
    doi: 10.1038/nrmicro.2017.27pubmed: 28420883google scholar: lookup
Subscribe to our newsletter
Join 99,824 horse owners like you who receive our email updates on horse health and nutrition.