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Genome research2015; 25(9); 1360-1371; doi: 10.1101/gr.189803.115

Genome specialization and decay of the strangles pathogen, Streptococcus equi, is driven by persistent infection.

Abstract: Strangles, the most frequently diagnosed infectious disease of horses worldwide, is caused by Streptococcus equi. Despite its prevalence, the global diversity and mechanisms underlying the evolution of S. equi as a host-restricted pathogen remain poorly understood. Here, we define the global population structure of this important pathogen and reveal a population replacement in the late 19th or early 20th Century. Our data reveal a dynamic genome that continues to mutate and decay, but also to amplify and acquire genes despite the organism having lost its natural competence and become host-restricted. The lifestyle of S. equi within the horse is defined by short-term acute disease, strangles, followed by long-term infection. Population analysis reveals evidence of convergent evolution in isolates from post-acute disease samples as a result of niche adaptation to persistent infection within a host. Mutations that lead to metabolic streamlining and the loss of virulence determinants are more frequently found in persistent isolates, suggesting that the pathogenic potential of S. equi reduces as a consequence of long-term residency within the horse post-acute disease. An example of this is the deletion of the equibactin siderophore locus that is associated with iron acquisition, which occurs exclusively in persistent isolates, and renders S. equi significantly less able to cause acute disease in the natural host. We identify several loci that may similarly be required for the full virulence of S. equi, directing future research toward the development of new vaccines against this host-restricted pathogen.
Publication Date: 2015-07-09 PubMed ID: 26160165PubMed Central: PMC4561494DOI: 10.1101/gr.189803.115Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research studies the global diversity and evolution of Streptococcus equi, the bacterium causing the most common infectious equine disease called strangles. The study reveals the bacterium continuously mutating and decaying, but still able to acquire and amplify genes. The research also highlights that as S. equi resides long-term within its horse host post-acute disease, its virulence reduces. Findings direct future study towards developing new vaccines against this pathogen.

Understanding the Global Population Structure of Streptococcus equi

  • The study aims to understand the global diversity and evolution process of the bacteria Streptococcus equi, which is the main cause of strangles, a common infectious disease in horses.
  • Through population analysis, researchers discerned a population shift in the late 19th or early 20th century. This pathogen has a dynamic genome that continues to mutate and decay. Despite losing its natural competence and becoming host-restricted, it still manages to acquire and amplify genes.

Niche Adaptation to Persistent Infection within a Host

  • The lifestyle of S. equi within the horse host is characterized by acute strangles disease, followed by a long-term infection. The researchers found evidence of convergent evolution in isolates culled from post-acute disease samples, indicating some form of adaptation to its host over an extended period of infection.
  • This adaptation often results in metabolic streamlining and a decrease in the bacterium’s virulence over time. Mutations that lead to these changes are found more frequently in persistent isolates, implying that the pathogenic potential of S. equi lessens as a result of long-term residency within the horse after the acute disease phase.

The Reduction of S. equi Virulence

  • In the course of long-term residency within the horse, S. equi loses some of its ability to cause acute disease. A significant example is the deletion of the equibactin siderophore locus, which is integral for iron acquisition.
  • This deletion, which exclusively occurs in persistent isolates, greatly reduces the bacterium’s ability to cause acute illness in the horse, suggesting the reduction of S. equi’s virulence over time.

Directions for Future Research

  • The research identified several loci that may be required for S. equi’s full virulence. This points to directions for future research focusing on these loci, with the aim of developing new vaccines to counter the disease caused by this host-restricted pathogen.

Cite This Article

APA
Harris SR, Robinson C, Steward KF, Webb KS, Paillot R, Parkhill J, Holden MT, Waller AS. (2015). Genome specialization and decay of the strangles pathogen, Streptococcus equi, is driven by persistent infection. Genome Res, 25(9), 1360-1371. https://doi.org/10.1101/gr.189803.115

Publication

ISSN: 1549-5469
NlmUniqueID: 9518021
Country: United States
Language: English
Volume: 25
Issue: 9
Pages: 1360-1371

Researcher Affiliations

Harris, Simon R
  • The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
Robinson, Carl
  • The Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom;
Steward, Karen F
  • The Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom;
Webb, Katy S
  • The Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom;
Paillot, Romain
  • The Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom;
Parkhill, Julian
  • The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
Holden, Matthew T G
  • The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; School of Medicine, University of St Andrews, North Haugh, St. Andrews KY16 9TF, United Kingdom.
Waller, Andrew S
  • The Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, United Kingdom;

MeSH Terms

  • Animals
  • Disease Outbreaks
  • Gene Amplification
  • Gene Deletion
  • Gene Order
  • Genetic Loci
  • Genome, Bacterial
  • Genomics / methods
  • Horse Diseases / epidemiology
  • Horse Diseases / microbiology
  • Horses
  • Host-Pathogen Interactions
  • Mutagenesis, Insertional
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Streptococcal Infections / veterinary
  • Streptococcus equi / classification
  • Streptococcus equi / genetics
  • United Kingdom / epidemiology

Grant Funding

  • Wellcome Trust
  • 098051 / Wellcome Trust

References

This article includes 57 references
  1. Anon. The strangles. 1831;pp. 149–151.
  2. Bazeley PL. Studies with equine streptococci 1. Aust Vet J 1940;16:140–146.
  3. Blaine D. Strangles. 1841;pp. 432–433.
  4. Borst LB, Patterson SK, Lanka S, Barger AM, Fredrickson RL, Maddox CW. Evaluation of a commercially available modified-live Streptococcus equi subsp equi vaccine in ponies.. Am J Vet Res 2011 Aug;72(8):1130-8.
    pubmed: 21801073doi: 10.2460/ajvr.72.8.1130google scholar: lookup
  5. Bryant JM, Schürch AC, van Deutekom H, Harris SR, de Beer JL, de Jager V, Kremer K, van Hijum SA, Siezen RJ, Borgdorff M, Bentley SD, Parkhill J, van Soolingen D. Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data.. BMC Infect Dis 2013 Feb 27;13:110.
    pmc: PMC3599118pubmed: 23446317doi: 10.1186/1471-2334-13-110google scholar: lookup
  6. Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O, Kontsevaya I, Corander J, Bryant J, Parkhill J, Nejentsev S, Horstmann RD, Brown T, Drobniewski F. Evolution and transmission of drug-resistant tuberculosis in a Russian population.. Nat Genet 2014 Mar;46(3):279-86.
    pmc: PMC3939361pubmed: 24464101doi: 10.1038/ng.2878google scholar: lookup
  7. Clabby BJ. A short history of the Royal Army Veterinary Corps.. Proc R Soc Med 1976 Feb;69(2):93-6.
    pmc: PMC1864482pubmed: 772681
  8. Corander J, Marttinen P, Sirén J, Tang J. Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations.. BMC Bioinformatics 2008 Dec 16;9:539.
    pmc: PMC2629778pubmed: 19087322doi: 10.1186/1471-2105-9-539google scholar: lookup
  9. Cornejo OE, Lefébure T, Bitar PD, Lang P, Richards VP, Eilertson K, Do T, Beighton D, Zeng L, Ahn SJ, Burne RA, Siepel A, Bustamante CD, Stanhope MJ. Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans.. Mol Biol Evol 2013 Apr;30(4):881-93.
    pmc: PMC3603310pubmed: 23228887doi: 10.1093/molbev/mss278google scholar: lookup
  10. Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J, van der Linden M, McGee L, von Gottberg A, Song JH, Ko KS, Pichon B, Baker S, Parry CM, Lambertsen LM, Shahinas D, Pillai DR, Mitchell TJ, Dougan G, Tomasz A, Klugman KP, Parkhill J, Hanage WP, Bentley SD. Rapid pneumococcal evolution in response to clinical interventions.. Science 2011 Jan 28;331(6016):430-4.
    pmc: PMC3648787pubmed: 21273480doi: 10.1126/science.1198545google scholar: lookup
  11. Darmstadt GL, Mentele L, Podbielski A, Rubens CE. Role of group A streptococcal virulence factors in adherence to keratinocytes.. Infect Immun 2000 Mar;68(3):1215-21.
  12. Davies MR, Holden MT, Coupland P, Chen JH, Venturini C, Barnett TC, Zakour NL, Tse H, Dougan G, Yuen KY, Walker MJ. Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance.. Nat Genet 2015 Jan;47(1):84-7.
    pubmed: 25401300doi: 10.1038/ng.3147google scholar: lookup
  13. Delcher AL, Phillippy A, Carlton J, Salzberg SL. Fast algorithms for large-scale genome alignment and comparison.. Nucleic Acids Res 2002 Jun 1;30(11):2478-83.
    pmc: PMC117189pubmed: 12034836doi: 10.1093/nar/30.11.2478google scholar: lookup
  14. Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees.. BMC Evol Biol 2007 Nov 8;7:214.
    pmc: PMC2247476pubmed: 17996036doi: 10.1186/1471-2148-7-214google scholar: lookup
  15. Firth C, Kitchen A, Shapiro B, Suchard MA, Holmes EC, Rambaut A. Using time-structured data to estimate evolutionary rates of double-stranded DNA viruses.. Mol Biol Evol 2010 Sep;27(9):2038-51.
    pmc: PMC3107591pubmed: 20363828doi: 10.1093/molbev/msq088google scholar: lookup
  16. Flores AR, Jewell BE, Fittipaldi N, Beres SB, Musser JM. Human disease isolates of serotype m4 and m22 group a streptococcus lack genes required for hyaluronic acid capsule biosynthesis.. mBio 2012 Nov 6;3(6):e00413-12.
    pmc: PMC3487777pubmed: 23131832doi: 10.1128/mbio.00413-12google scholar: lookup
  17. Graham MR, Smoot LM, Migliaccio CA, Virtaneva K, Sturdevant DE, Porcella SF, Federle MJ, Adams GJ, Scott JR, Musser JM. Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.. Proc Natl Acad Sci U S A 2002 Oct 15;99(21):13855-60.
    pmc: PMC129787pubmed: 12370433doi: 10.1073/pnas.202353699google scholar: lookup
  18. Guss B, Flock M, Frykberg L, Waller AS, Robinson C, Smith KC, Flock JI. Getting to grips with strangles: an effective multi-component recombinant vaccine for the protection of horses from Streptococcus equi infection.. PLoS Pathog 2009 Sep;5(9):e1000584.
  19. 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
  20. Harper M, Lee CJ. Genome-wide analysis of mutagenesis bias and context sensitivity of N-methyl-N'-nitro-N-nitrosoguanidine (NTG).. Mutat Res 2012 Mar 1;731(1-2):64-7.
    pubmed: 22080106doi: 10.1016/j.mrfmmm.2011.10.011google scholar: lookup
  21. Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA, Edgeworth JD, de Lencastre H, Parkhill J, Peacock SJ, Bentley SD. Evolution of MRSA during hospital transmission and intercontinental spread.. Science 2010 Jan 22;327(5964):469-74.
    pmc: PMC2821690pubmed: 20093474doi: 10.1126/science.1182395google scholar: lookup
  22. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, D'Arc S, Brazier J, Brown D, Coia JE, Douce G, Gerding D, Kim HJ, Koh TH, Kato H, Senoh M, Louie T, Michell S, Butt E, Peacock SJ, Brown NM, Riley T, Songer G, Wilcox M, Pirmohamed M, Kuijper E, Hawkey P, Wren BW, Dougan G, Parkhill J, Lawley TD. Emergence and global spread of epidemic healthcare-associated Clostridium difficile.. Nat Genet 2013 Jan;45(1):109-13.
    pmc: PMC3605770pubmed: 23222960doi: 10.1038/ng.2478google scholar: lookup
  23. Heather Z, Holden MT, Steward KF, Parkhill J, Song L, Challis GL, Robinson C, Davis-Poynter N, Waller AS. A novel streptococcal integrative conjugative element involved in iron acquisition.. Mol Microbiol 2008 Dec;70(5):1274-92.
  24. Herbeck JT, Nickle DC, Learn GH, Gottlieb GS, Curlin ME, Heath L, Mullins JI. Human immunodeficiency virus type 1 env evolves toward ancestral states upon transmission to a new host.. J Virol 2006 Feb;80(4):1637-44.
  25. 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.
  26. Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, Strommenger B, Layer F, Witte W, de Lencastre H, Skov R, Westh H, Zemlicková H, Coombs G, Kearns AM, Hill RL, Edgeworth J, Gould I, Gant V, Cooke J, Edwards GF, McAdam PR, Templeton KE, McCann A, Zhou Z, Castillo-Ramírez S, Feil EJ, Hudson LO, Enright MC, Balloux F, Aanensen DM, Spratt BG, Fitzgerald JR, Parkhill J, Achtman M, Bentley SD, Nübel U. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.. Genome Res 2013 Apr;23(4):653-64.
    pmc: PMC3613582pubmed: 23299977doi: 10.1101/gr.147710.112google scholar: lookup
  27. Jacobs AA, Goovaerts D, Nuijten PJ, Theelen RP, Hartford OM, Foster TJ. Investigations towards an efficacious and safe strangles vaccine: submucosal vaccination with a live attenuated Streptococcus equi.. Vet Rec 2000 Nov 11;147(20):563-7.
    pubmed: 11104039doi: 10.1136/vr.147.20.563google scholar: lookup
  28. Kelly C, Bugg M, Robinson C, Mitchell Z, Davis-Poynter N, Newton JR, Jolley KA, Maiden MC, Waller AS. Sequence variation of the SeM gene of Streptococcus equi allows discrimination of the source of strangles outbreaks.. J Clin Microbiol 2006 Feb;44(2):480-6.
  29. Lefébure T, Richards VP, Lang P, Pavinski-Bitar P, Stanhope MJ. Gene repertoire evolution of Streptococcus pyogenes inferred from phylogenomic analysis with Streptococcus canis and Streptococcus dysgalactiae.. PLoS One 2012;7(5):e37607.
  30. Lemey P, Rambaut A, Pybus OG. HIV evolutionary dynamics within and among hosts.. AIDS Rev 2006 Jul-Sep;8(3):125-40.
    pubmed: 17078483
  31. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. The Sequence Alignment/Map format and SAMtools.. Bioinformatics 2009 Aug 15;25(16):2078-9.
  32. Lythgoe KA, Fraser C. New insights into the evolutionary rate of HIV-1 at the within-host and epidemiological levels.. Proc Biol Sci 2012 Aug 22;279(1741):3367-75.
    pmc: PMC3385732pubmed: 22593106doi: 10.1098/rspb.2012.0595google scholar: lookup
  33. Marttinen P, Hanage WP, Croucher NJ, Connor TR, Harris SR, Bentley SD, Corander J. Detection of recombination events in bacterial genomes from large population samples.. Nucleic Acids Res 2012 Jan;40(1):e6.
    pmc: PMC3245952pubmed: 22064866doi: 10.1093/nar/gkr928google scholar: lookup
  34. Miles WJ. Strangles. 1868;Vol. 3, pp. 290–291.
  35. Newton JR, Wood JL, Dunn KA, DeBrauwere MN, Chanter N. Naturally occurring persistent and asymptomatic infection of the guttural pouches of horses with Streptococcus equi.. Vet Rec 1997 Jan 25;140(4):84-90.
    pubmed: 9032908doi: 10.1136/vr.140.4.84google scholar: lookup
  36. Newton JR, Verheyen K, Talbot NC, Timoney JF, Wood JL, Lakhani KH, Chanter N. Control of strangles outbreaks by isolation of guttural pouch carriers identified using PCR and culture of Streptococcus equi.. Equine Vet J 2000 Nov;32(6):515-26.
    pubmed: 11093626doi: 10.2746/042516400777584721google scholar: lookup
  37. Patty OA, Cursons RT. The molecular identification of Streptococcus equi subsp. equi strains isolated within New Zealand.. N Z Vet J 2014 Mar;62(2):63-7.
    pubmed: 24151876doi: 10.1080/00480169.2013.841536google scholar: lookup
  38. Quail MA, Otto TD, Gu Y, Harris SR, Skelly TF, McQuillan JA, Swerdlow HP, Oyola SO. Optimal enzymes for amplifying sequencing libraries.. Nat Methods 2011 Dec 28;9(1):10-1.
    pubmed: 22205512doi: 10.1038/nmeth.1814google scholar: lookup
  39. Ruffus J. nDe Medicina Equorum. 1251.
  40. Schrager HM, Rheinwald JG, Wessels MR. Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection.. J Clin Invest 1996 Nov 1;98(9):1954-8.
    pmc: PMC507637pubmed: 8903312doi: 10.1172/jci118998google scholar: lookup
  41. Schütz JW. The streptococcus of strangles. J Comp Pathol Therap 1888;1:191–208.
  42. Shea PR, Beres SB, Flores AR, Ewbank AL, Gonzalez-Lugo JH, Martagon-Rosado AJ, Martinez-Gutierrez JC, Rehman HA, Serrano-Gonzalez M, Fittipaldi N, Ayers SD, Webb P, Willey BM, Low DE, Musser JM. Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations.. Proc Natl Acad Sci U S A 2011 Mar 22;108(12):5039-44.
    pmc: PMC3064369pubmed: 21383167doi: 10.1073/pnas.1016282108google scholar: lookup
  43. Solleysel J. Le parfait maréchal. 1664.
  44. Stamatakis A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models.. Bioinformatics 2006 Nov 1;22(21):2688-90.
    pubmed: 16928733doi: 10.1093/bioinformatics/btl446google scholar: lookup
  45. Sun G, Luo T, Yang C, Dong X, Li J, Zhu Y, Zheng H, Tian W, Wang S, Barry CE 3rd, Mei J, Gao Q. Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients.. J Infect Dis 2012 Dec 1;206(11):1724-33.
    pmc: PMC3488197pubmed: 22984115doi: 10.1093/infdis/jis601google scholar: lookup
  46. Timoney JF. Protection of equines against Streptococcus equi. 1985.
  47. Todd AG. Strangles. J Comp Pathol Therap 1910;23:212–229.
  48. Viterbi AJ. Error bounds for convolutional codes and an asymptotically optimum decoding algorithm. IEEE Trans Inf Theory 1967;13:260–269.
  49. Walker JA, Timoney JF. Construction of a stable non-mucoid deletion mutant of the Streptococcus equi Pinnacle vaccine strain.. Vet Microbiol 2002 Nov 6;89(4):311-21.
    pubmed: 12383640doi: 10.1016/s0378-1135(02)00205-5google scholar: lookup
  50. Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, Eyre DW, Wilson DJ, Hawkey PM, Crook DW, Parkhill J, Harris D, Walker AS, Bowden R, Monk P, Smith EG, Peto TE. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study.. Lancet Infect Dis 2013 Feb;13(2):137-46.
  51. Waller AS, Robinson C. Streptococcus zooepidemicus and Streptococcus equi evolution: the role of CRISPRs.. Biochem Soc Trans 2013 Dec;41(6):1437-43.
    pubmed: 24256234doi: 10.1042/bst20130165google scholar: lookup
  52. 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
  53. White J. Strangles. 1825;pp. 180–181.
  54. White J, Spooner WC. Strangles. 1842;pp. 129–131.
  55. Williams W. Febra pyogenica, or strangles. 1884;pp. 43–51.
  56. Ye K, Schulz MH, Long Q, Apweiler R, Ning Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads.. Bioinformatics 2009 Nov 1;25(21):2865-71.
  57. Zerbino DR, Birney E. Velvet: algorithms for de novo short read assembly using de Bruijn graphs.. Genome Res 2008 May;18(5):821-9.
    pmc: PMC2336801pubmed: 18349386doi: 10.1101/gr.074492.107google scholar: lookup

Citations

This article has been cited 35 times.