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Infection and immunity2010; 78(4); 1728-1739; doi: 10.1128/IAI.01079-09

Contribution of each of four Superantigens to Streptococcus equi-induced mitogenicity, gamma interferon synthesis, and immunity.

Abstract: Streptococcus equi is the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death. S. equi produces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins of Streptococcus pyogenes. The aim of this study was to characterize the contribution of each of these S. equi sAgs to mitogenic activity in vitro and quantify the sAg-neutralizing capacity of sera from naturally infected horses in order to better understand their role in pathogenicity. Each of the sAgs was successfully cloned, and soluble proteins were produced in Escherichia coli. SeeI, SeeL, and SeeM induced a dose-dependent proliferative response in equine CD4 T lymphocytes and synthesis of gamma interferon (IFN-gamma). SeeH did not stimulate equine peripheral blood mononuclear cells (PBMC) but induced proliferation of asinine PBMC. Allelic replacement mutants of S. equi strain 4047 with sequential deletion of the superantigen genes were generated. Deletion of seeI, seeL, and seeM completely abrogated the mitogenic activity and synthesis of IFN-gamma, in equine PBMC, of the strain 4047 culture supernatant. Sera from naturally infected convalescent horses had only limited sAg-neutralizing activities. We propose that S. equi sAgs play an important role in S. equi pathogenicity by stimulating an overzealous and inappropriate Th1 response that may interfere with the development of an effective immune response.
Publication Date: 2010-02-01 PubMed ID: 20123710PubMed Central: PMC2849420DOI: 10.1128/IAI.01079-09Google 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.

The study explored the role of four different superantigens produced by the bacteria called Streptococcus equi, which causes a common and severe horse disease known as strangles. The research revealed how each superantigen contributes to the disease’s development and the immune response it triggers in horses.

About Streptococcus equi and Strangles

  • Streptococcus equi is responsible for strangles, a highly infectious disease that primarily affects horses.
  • Strangles is characterized by swelling and formation of abscesses in the lymph nodes of the horse’s head and neck, which could potentially strangle the horse to death.
  • The bacteria produce four superantigens, termed SeeH, SeeI, SeeL, and SeeM. These superantigens are similar to the toxins produced by another bacteria, Streptococcus pyogenes.

Research Aim and Methodology

  • The research aimed to understand each superantigen’s role in disease development and the immune response it triggers.
  • Scientists cloned each of the superantigens and produced them as soluble proteins in the bacterium Escherichia coli for their experiments.

Findings of the Study

  • Three superantigens, SeeI, SeeL, and SeeM, were found to induce a dose-dependent increase in the proliferation of CD4 T lymphocytes, a type of white blood cell, in horses, along with the synthesis of an immune-response protein called gamma interferon.
  • However, the SeeH superantigen did not show any significant stimulatory impact on horse white blood cells but was active in asinine (donkey family) white blood cells.
  • When these superantigen genes were deleted from the bacterial strain, it resulted in loss of disease-causing ability and synthesis of gamma interferon, confirming the role of these superantigens in the disease development.
  • Blood serum from horses that had recovered from the infection demonstrated only limited potential to neutralize these superantigens.

Conclusions of the Study

  • The study concluded that the superantigens produced by Streptococcus equi play a critical role in pathogenicity by triggering an aggressive and inappropriate immune response.
  • This excessive immune response could be interfering with the development of an effective immune response and thus be a key factor in the severity and progression of the disease.

Cite This Article

APA
Paillot R, Robinson C, Steward K, Wright N, Jourdan T, Butcher N, Heather Z, Waller AS. (2010). Contribution of each of four Superantigens to Streptococcus equi-induced mitogenicity, gamma interferon synthesis, and immunity. Infect Immun, 78(4), 1728-1739. https://doi.org/10.1128/IAI.01079-09

Publication

ISSN: 1098-5522
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 78
Issue: 4
Pages: 1728-1739

Researcher Affiliations

Paillot, Romain
  • Animal Health Trust, Centre for Preventive Medicine, Lanwades Park, Newmarket, Suffolk CB8 7UU, United Kingdom. romain.paillot@aht.org.uk
Robinson, Carl
    Steward, Karen
      Wright, Nicola
        Jourdan, Thibaud
          Butcher, Nicola
            Heather, Zoe
              Waller, Andrew S

                MeSH Terms

                • Animals
                • Antibodies, Bacterial / blood
                • Antibodies, Neutralizing / blood
                • Antigens, Bacterial / genetics
                • Antigens, Bacterial / immunology
                • Cell Proliferation
                • Cells, Cultured
                • Gene Knockout Techniques
                • Horses
                • Interferon-gamma / biosynthesis
                • Leukocytes, Mononuclear / immunology
                • Streptococcus equi / immunology
                • Superantigens / genetics
                • Superantigens / immunology

                References

                This article includes 37 references
                1. Alber J, El-Sayed A, Estoepangestie S, Lämmler C, Zschöck M. Dissemination of the superantigen encoding genes seeL, seeM, szeL and szeM in Streptococcus equi subsp. equi and Streptococcus equi subsp. zooepidemicus.. Vet Microbiol 2005 Aug 10;109(1-2):135-41.
                  pubmed: 15953700doi: 10.1016/j.vetmic.2005.05.001google scholar: lookup
                2. Anzai T, Sheoran AS, Kuwamoto Y, Kondo T, Wada R, Inoue T, Timoney JF. Streptococcus equi but not Streptococcus zooepidemicus produces potent mitogenic responses from equine peripheral blood mononuclear cells.. Vet Immunol Immunopathol 1999 Feb 22;67(3):235-46.
                  pubmed: 10195462doi: 10.1016/s0165-2427(98)00227-xgoogle scholar: lookup
                3. Arad G, Hillman D, Levy R, Kaempfer R. Broad-spectrum immunity against superantigens is elicited in mice protected from lethal shock by a superantigen antagonist peptide.. Immunol Lett 2004 Feb 15;91(2-3):141-5.
                  pubmed: 15019282doi: 10.1016/j.imlet.2003.11.003google scholar: lookup
                4. Arad G, Hillman D, Levy R, Kaempfer R. Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock.. J Leukoc Biol 2001 Jun;69(6):921-7.
                  pubmed: 11404377
                5. Artiushin SC, Timoney JF, Sheoran AS, Muthupalani SK. Characterization and immunogenicity of pyrogenic mitogens SePE-H and SePE-I of Streptococcus equi.. Microb Pathog 2002 Feb;32(2):71-85.
                  pubmed: 11812213doi: 10.1006/mpat.2001.0482google scholar: lookup
                6. Chanter N. Streptococci and enterococci as animal pathogens.. Soc Appl Bacteriol Symp Ser 1997;26:100S-109S.
                  pubmed: 9436322
                7. Dellabona P, Peccoud J, Kappler J, Marrack P, Benoist C, Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove.. Cell 1990 Sep 21;62(6):1115-21.
                  pubmed: 2401011doi: 10.1016/0092-8674(90)90388-ugoogle scholar: lookup
                8. Hamilton A, Robinson C, Sutcliffe IC, Slater J, Maskell DJ, Davis-Poynter N, Smith K, Waller A, Harrington DJ. Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus equi to a greater extent than does loss of general lipoprotein lipidation.. Infect Immun 2006 Dec;74(12):6907-19.
                  pmc: PMC1698103pubmed: 17015455doi: 10.1128/IAI.01116-06google scholar: lookup
                9. Hines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC. Clearance of virulent but not avirulent Rhodococcus equi from the lungs of adult horses is associated with intracytoplasmic gamma interferon production by CD4+ and CD8+ T lymphocytes.. Clin Diagn Lab Immunol 2003 Mar;10(2):208-15.
                10. Holden MT, Heather Z, Paillot R, Steward KF, Webb K, Ainslie F, Jourdan T, Bason NC, Holroyd NE, Mungall K, Quail MA, Sanders M, Simmonds M, Willey D, Brooks K, Aanensen DM, Spratt BG, Jolley KA, Maiden MC, Kehoe M, Chanter N, Bentley SD, Robinson C, Maskell DJ, Parkhill J, Waller AS. Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.. PLoS Pathog 2009 Mar;5(3):e1000346.
                11. Kotb M, Norrby-Teglund A, McGeer A, El-Sherbini H, Dorak MT, Khurshid A, Green K, Peeples J, Wade J, Thomson G, Schwartz B, Low DE. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections.. Nat Med 2002 Dec;8(12):1398-404.
                  pubmed: 12436116doi: 10.1038/nm1202-800google scholar: lookup
                12. Kydd J, Antczak DF, Allen WR, Barbis D, Butcher G, Davis W, Duffus WP, Edington N, Grünig G, Holmes MA. Report of the First International Workshop on Equine Leucocyte Antigens, Cambridge, UK, July 1991.. Vet Immunol Immunopathol 1994 Jul;42(1):3-60.
                  pubmed: 7975180doi: 10.1016/0165-2427(94)90088-4google scholar: lookup
                13. Li H, Llera A, Malchiodi EL, Mariuzza RA. The structural basis of T cell activation by superantigens.. Annu Rev Immunol 1999;17:435-66.
                14. Llewelyn M, Cohen J. Superantigens: microbial agents that corrupt immunity.. Lancet Infect Dis 2002 Mar;2(3):156-62.
                  pubmed: 11944185doi: 10.1016/s1473-3099(02)00222-0google scholar: lookup
                15. Llewelyn M, Sriskandan S, Peakman M, Ambrozak DR, Douek DC, Kwok WW, Cohen J, Altmann DM. HLA class II polymorphisms determine responses to bacterial superantigens.. J Immunol 2004 Feb 1;172(3):1719-26.
                  pubmed: 14734754doi: 10.4049/jimmunol.172.3.1719google scholar: lookup
                16. Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA. Identification of pulmonary T-lymphocyte and serum antibody isotype responses associated with protection against Rhodococcus equi.. Clin Diagn Lab Immunol 2002 Nov;9(6):1270-6.
                17. Luce R, Shepherd M, Paillot R, Blacklawst B, Wood JL, Kydd JH. Equine herpesvirus-1-specific interferon gamma (IFNgamma) synthesis by peripheral blood mononuclear cells in thoroughbred horses.. Equine Vet J 2007 May;39(3):202-9.
                  pubmed: 17520969doi: 10.2746/042516407x174216google scholar: lookup
                18. Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O'Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.. Vet Immunol Immunopathol 1998 Mar 31;62(2):101-43.
                  pubmed: 9638857doi: 10.1016/s0165-2427(97)00160-8google scholar: lookup
                19. Maguin E, Prévost H, Ehrlich SD, Gruss A. Efficient insertional mutagenesis in lactococci and other gram-positive bacteria.. J Bacteriol 1996 Feb;178(3):931-5.
                  pmc: PMC177749pubmed: 8550537doi: 10.1128/jb.178.3.931-935.1996google scholar: lookup
                20. McCormick JK, Pragman AA, Stolpa JC, Leung DY, Schlievert PM. Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen.. Infect Immun 2001 Mar;69(3):1381-8.
                21. Norrby-Teglund A, Norgren M, Holm SE, Andersson U, Andersson J. Similar cytokine induction profiles of a novel streptococcal exotoxin, MF, and pyrogenic exotoxins A and B.. Infect Immun 1994 Sep;62(9):3731-8.
                22. Paillot R, Daly JM, Juillard V, Minke JM, Hannant D, Kydd JH. Equine interferon gamma synthesis in lymphocytes after in vivo infection and in vitro stimulation with EHV-1.. Vaccine 2005 Aug 22;23(36):4541-51.
                  pubmed: 15913852doi: 10.1016/j.vaccine.2005.03.048google scholar: lookup
                23. Paillot R, Daly JM, Luce R, Montesso F, Davis-Poynter N, Hannant D, Kydd JH. Frequency and phenotype of EHV-1 specific, IFN-gamma synthesising lymphocytes in ponies: the effects of age, pregnancy and infection.. Dev Comp Immunol 2007;31(2):202-14.
                  pubmed: 16824599doi: 10.1016/j.dci.2006.05.010google scholar: lookup
                24. Paillot R, Kydd JH, MacRae S, Minke JM, Hannant D, Daly JM. New assays to measure equine influenza virus-specific Type 1 immunity in horses.. Vaccine 2007 Oct 16;25(42):7385-98.
                  pubmed: 17881098doi: 10.1016/j.vaccine.2007.08.033google scholar: lookup
                25. Proft T, Fraser JD. Bacterial superantigens.. Clin Exp Immunol 2003 Sep;133(3):299-306.
                26. Proft T, Webb PD, Handley V, Fraser JD. Two novel superantigens found in both group A and group C Streptococcus.. Infect Immun 2003 Mar;71(3):1361-9.
                27. Simon D, Ferretti JJ. Electrotransformation of Streptococcus pyogenes with plasmid and linear DNA.. FEMS Microbiol Lett 1991 Aug 1;66(2):219-24.
                  pubmed: 1936949doi: 10.1016/0378-1097(91)90336-9google scholar: lookup
                28. Slater JD. Strangles, bastard strangles, vives and glanders: archaeological relics in a genomic age.. Equine Vet J 2003 Mar;35(2):118-20.
                  pubmed: 12638785doi: 10.2746/042516403776114252google scholar: lookup
                29. Smoot LM, McCormick JK, Smoot JC, Hoe NP, Strickland I, Cole RL, Barbian KD, Earhart CA, Ohlendorf DH, Veasy LG, Hill HR, Leung DY, Schlievert PM, Musser JM. Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks.. Infect Immun 2002 Dec;70(12):7095-104.
                30. Sriskandan S, Evans TJ, Cohen J. Bacterial superantigen-induced human lymphocyte responses are nitric oxide dependent and mediated by IL-12 and IFN-gamma.. J Immunol 1996 Apr 1;156(7):2430-5.
                  pubmed: 8786301
                31. Sriskandan S, Faulkner L, Hopkins P. Streptococcus pyogenes: Insight into the function of the streptococcal superantigens.. Int J Biochem Cell Biol 2007;39(1):12-9.
                  pubmed: 17029999doi: 10.1016/j.biocel.2006.08.009google scholar: lookup
                32. Takata Y, Seki S, Dobashi H, Takeshita S, Nakatani K, Kamezawa Y, Hiraide H, Sekine I, Yoshioka S. Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD).. Clin Exp Immunol 1998 Nov;114(2):311-9.
                33. Timoney JF. The pathogenic equine streptococci.. Vet Res 2004 Jul-Aug;35(4):397-409.
                  pubmed: 15236673doi: 10.1051/vetres:2004025google scholar: lookup
                34. Timoney JF. Strangles.. Vet Clin North Am Equine Pract 1993 Aug;9(2):365-74.
                  pubmed: 8358649doi: 10.1016/s0749-0739(17)30403-0google scholar: lookup
                35. Unnikrishnan M, Altmann DM, Proft T, Wahid F, Cohen J, Fraser JD, Sriskandan S. The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes.. J Immunol 2002 Sep 1;169(5):2561-9.
                  pubmed: 12193726doi: 10.4049/jimmunol.169.5.2561google scholar: lookup
                36. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
                  pmc: PMC3785132pubmed: 19892987doi: 10.1126/science.1178158google scholar: lookup
                37. Webb K, Jolley KA, Mitchell Z, Robinson C, Newton JR, Maiden MCJ, Waller A. Development of an unambiguous and discriminatory multilocus sequence typing scheme for the Streptococcus zooepidemicus group.. Microbiology (Reading) 2008 Oct;154(Pt 10):3016-3024.
                  pubmed: 18832307doi: 10.1099/mic.0.2008/018911-0google scholar: lookup

                Citations

                This article has been cited 18 times.
                1. Morris ERA, Wu J, Bordin AI, Lawhon SD, Cohen ND. Differences in the Accessory Genomes and Methylomes of Strains of Streptococcus equi subsp. equi and of Streptococcus equi subsp. zooepidemicus Obtained from the Respiratory Tract of Horses from Texas. Microbiol Spectr 2022 Feb 23;10(1):e0076421.
                  doi: 10.1128/spectrum.00764-21pubmed: 35019696google scholar: lookup
                2. Frosth S, Morris ERA, Wilson H, Frykberg L, Jacobsson K, Parkhill J, Flock JI, Wood T, Guss B, Aanensen DM, Boyle AG, Riihimäki M, Cohen ND, Waller AS. Conservation of vaccine antigen sequences encoded by sequenced strains of Streptococcus equi subsp. equi. Equine Vet J 2023 Jan;55(1):92-101.
                  doi: 10.1111/evj.13552pubmed: 35000217google scholar: lookup
                3. Dominguez-Medina CC, Rash NL, Robillard S, Robinson C, Efstratiou A, Broughton K, Parkhill J, Holden MTG, Lopez-Alvarez MR, Paillot R, Waller AS. SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles. Int J Mol Sci 2020 Jun 23;21(12).
                  doi: 10.3390/ijms21124467pubmed: 32586031google scholar: lookup
                4. von Beek C, Waern I, Eriksson J, Melo FR, Robinson C, Waller AS, Sellin ME, Guss B, Pejler G. Streptococcal sagA activates a proinflammatory response in mast cells by a sublytic mechanism. Cell Microbiol 2019 Sep;21(9):e13064.
                  doi: 10.1111/cmi.13064pubmed: 31155820google scholar: lookup
                5. Neamat-Allah AN, Damaty HM. Strangles in Arabian horses in Egypt: Clinical, epidemiological, hematological, and biochemical aspects. Vet World 2016 Aug;9(8):820-6.
                6. Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ. Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro. Stem Cell Res Ther 2014 Jul 30;5(4):90.
                  doi: 10.1186/scrt479pubmed: 25080326google scholar: lookup
                7. Pelkonen S, Lindahl SB, Suomala P, Karhukorpi J, Vuorinen S, Koivula I, Väisänen T, Pentikäinen J, Autio T, Tuuminen T. Transmission of Streptococcus equi subspecies zooepidemicus infection from horses to humans. Emerg Infect Dis 2013 Jul;19(7):1041-8.
                  doi: 10.3201/eid1907.121365pubmed: 23777752google scholar: lookup
                8. Lachance C, Gottschalk M, Gerber PP, Lemire P, Xu J, Segura M. Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis. Infect Immun 2013 Jun;81(6):1928-39.
                  doi: 10.1128/IAI.01317-12pubmed: 23509145google scholar: lookup
                9. Webb K, Barker C, Harrison T, Heather Z, Steward KF, Robinson C, Newton JR, Waller AS. Detection of Streptococcus equi subspecies equi using a triplex qPCR assay. Vet J 2013 Mar;195(3):300-4.
                  doi: 10.1016/j.tvjl.2012.07.007pubmed: 22884566google scholar: lookup
                10. Priestnall SL, Erles K, Brooks HW, Cardwell JM, Waller AS, Paillot R, Robinson C, Darby AC, Holden MT, Schöniger S. Characterization of pneumonia due to Streptococcus equi subsp. zooepidemicus in dogs. Clin Vaccine Immunol 2010 Nov;17(11):1790-6.
                  doi: 10.1128/CVI.00188-10pubmed: 20861329google scholar: lookup
                11. Paillot R, Darby AC, Robinson C, Wright NL, Steward KF, Anderson E, Webb K, Holden MT, Efstratiou A, Broughton K, Jolley KA, Priestnall SL, Marotti Campi MC, Hughes MA, Radford A, Erles K, Waller AS. Identification of three novel superantigen-encoding genes in Streptococcus equi subsp. zooepidemicus, szeF, szeN, and szeP. Infect Immun 2010 Nov;78(11):4817-27.
                  doi: 10.1128/IAI.00751-10pubmed: 20713629google scholar: lookup
                12. He L, Khine NO, Song J, Loubière C, Butaye P. Geographic diversity of the Streptococcus equi subsp. equi accessory genome: implications for vaccines and global surveillance. Front Vet Sci 2025;12:1721958.
                  doi: 10.3389/fvets.2025.1721958pubmed: 41394906google scholar: lookup
                13. Gröndahl G, Righetti F, Aspán A, Bjerketorp J, Frosth S, Frykberg L, Jacobsson K, Guss B, Paillot R, Flock JI, Henriques-Normark B, Waller AS. Reining in strangles: Absence of disease in horses vaccinated with a DIVA-compatible recombinant fusion protein vaccine, Strangvac, following natural exposure to Streptococcus equi subspecies equi. Equine Vet J 2026 Mar;58(2):476-485.
                  doi: 10.1111/evj.70125pubmed: 41276995google scholar: lookup
                14. Sukmanadi M, Khairullah AR, Wardhani BWK, Mustofa I, Aliyah SH, Moses IB, Ahmad RZ, Khalisa AT, Pratama BP, Kusala MKJ, Kurniasih DAA, Akintunde AO, Fauziah I, Wibowo S, Furqoni AH, Fauzia KA, Melati I, Kurniawan M'. Glanders: Historical military use and potential bioterrorism concern. Open Vet J 2025 Sep;15(9):3912-3930.
                  doi: 10.5455/OVJ.2025.v15.i9.1pubmed: 41200364google scholar: lookup
                15. McLinden LA, Kemp-Symonds JG, Daly JM, Blanchard AM, Waller AS, Freeman SL. Effectiveness of a screening protocol employed at a UK rescue centre to prevent introduction of strangles. Equine Vet J 2026 Mar;58(2):466-475.
                  doi: 10.1111/evj.70080pubmed: 41031843google scholar: lookup
                16. Wilson HJ, Dong J, van Tonder AJ, Ruis C, Lefrancq N, McGlennon A, Bustos C, Frosth S, Léon A, Blanchard AM, Holden M, Waller AS, Parkhill J. Progressive evolution of Streptococcus equi from Streptococcus equi subsp. zooepidemicus and adaption to equine hosts. Microb Genom 2025 Mar;11(3).
                  doi: 10.1099/mgen.0.001366pubmed: 40152912google scholar: lookup
                17. Nakajima K, Kasuya K, Senba H, Tagami K, Kinoshita Y, Niwa H. Genetic analysis based on next generation sequencing of Streptococcus equi subsp. equi isolated from horses imported into Japan. J Vet Med Sci 2024 Aug 2;86(8):828-832.
                  doi: 10.1292/jvms.23-0342pubmed: 38897953google scholar: lookup
                18. Chen X, Mou K, Lu W, Schumacher L, Resende-De-Macedo N, Sitthicharoenchai P, Derscheid R, Burrough E, Li G. Genomic characterization of Streptococcus equi subspecies zooepidemicus from a 2021 outbreak in Indiana with increased sow mortality. mSphere 2023 Dec 20;8(6):e0040423.
                  doi: 10.1128/msphere.00404-23pubmed: 37861318google scholar: lookup