Analyze Diet
Clinical and vaccine immunology : CVI2013; 20(8); 1181-1188; doi: 10.1128/CVI.00069-13

Characterization and protective immunogenicity of the SzM protein of Streptococcus zooepidemicus NC78 from a clonal outbreak of equine respiratory disease.

Abstract: Streptococcus zooepidemicus of Lancefield group C is a highly variable tonsillar and mucosal commensal that usually is associated with opportunistic infections of the respiratory tract of vertebrate hosts. More-virulent clones have caused epizootics of severe respiratory disease in dogs and horses. The virulence factors of these strains are poorly understood. The antiphagocytic protein SeM is a major virulence factor and protective antigen of Streptococcus equi, a clonal biovar of an ancestral S. zooepidemicus strain. Although the genome of S. zooepidemicus strain H70, an equine isolate, contains a partial homolog (szm) of sem, expression of the gene has not been documented. We have identified and characterized SzM from an encapsulated S. zooepidemicus strain from an epizootic of equine respiratory disease in New Caledonia. The SzM protein of strain NC78 (SzM(NC78)) has a predicted predominantly alpha-helical fibrillar structure with an LPSTG cell surface anchor motif and resistance to hot acid. A putative binding site for plasminogen is present in the B repeat region, the sequence of which shares homology with repeats of the plasminogen binding proteins of human group C and G streptococci. Equine plasminogen is activated in a dose-dependent manner by recombinant SzM(NC78). Only 23.20 and 25.46% DNA homology is shared with SeM proteins of S. equi strains CF32 and 4047, respectively, and homology ranges from 19.60 to 54.70% for SzM proteins of other S. zooepidemicus strains. As expected, SzM(NC78) reacted with convalescent-phase sera from horses with respiratory disease associated with strains of S. zooepidemicus. SzM(NC78) resembles SeM in binding equine fibrinogen and eliciting strong protective antibody responses in mice. Sera of vaccinated mice opsonized S. zooepidemicus strains NC78 and W60, the SzM protein of which shared partial amino acid homology with SzM(NC78). We conclude that SzM is a protective antigen of NC78; it was strongly reactive with serum antibodies from horses during recovery from S. zooepidemicus-associated respiratory disease.
Publication Date: 2013-06-05 PubMed ID: 23740925PubMed Central: PMC3754524DOI: 10.1128/CVI.00069-13Google 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.
  • 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 investigates the characteristics and immunogenic properties of a protein identified in a strain of Streptococcus zooepidemicus (S. zooepidemicus) found in equines suffering from respiratory diseases. The primary finding is that the protein, named SzM, shows protective capabilities against the strain, suggesting its potential use for disease prevention.

Investigation of SzM Protein

The researchers examined SzM, a protein found in S. zooepidemicus, a bacterium typically associated with respiratory tract infections in vertebrates. The strain studied was isolated from an outbreak of a respiratory disease in horses in New Caledonia. The structure of the protein was found to be predominantly alpha-helical and possesses various features, including a cell surface anchor motif and resistance to high temperatures and acidic conditions.

  • The SzM protein also exhibits a potential binding site for plasminogen, a vital enzyme involved in the breakdown of blood clots. The sequence of this region shows similarities with the plasminogen-binding proteins of certain human streptococcal bacteria.
  • The researchers further found that equine plasminogen activation is influenced by the presence of the SzM protein – an activity that increases with the raised amount of the protein.

Comparative Analysis and Reactivity

A comparative study was undertaken to ascertain the relationship between the SzM protein of S. zooepidemicus NC78 strain and the proteins of other associated strains. The results show that the level of shared DNA with other SeM proteins of the S. equi strains was relatively low, ranging around 23.20% and 25.46% for strains CF32 and 4047, respectively. There was an even wider range of homology amongst SzM proteins of other S. zooepidemicus strains – from 19.60% to 54.70%.

  • The SzM protein proved reactive with antibodies in the sera of horses recovering from a respiratory disease associated with S. zooepidemicus.

Vaccination Research Results

The protein’s protective capabilities were tested by exposing mice to it. The SzM protein was successful in eliciting a strong protective antibody response in the mice, similar to the SeM protein’s reaction with equine fibrinogen. These antibodies in the vaccinated mice’s sera were then found to opsonize, or mark for destruction, two strains of S. zooepidemicus, including the NC78 strain where the SzM protein was first identified. This was especially significant in cases where the enzyme exhibited partial amino acid homology with the SzM protein in the NC78 strain.

The results point toward the protein being a protective antigen for the NC78 strain, given its strong reactivity with the serum antibodies of horses during recovery from the associated respiratory disease. This suggests the potential use of SzM as a vaccine, which could enhance a horse’s immune system response to S. zooepidemicus infection, providing a promising avenue for future research.

Cite This Article

APA
Velineni S, Timoney JF. (2013). Characterization and protective immunogenicity of the SzM protein of Streptococcus zooepidemicus NC78 from a clonal outbreak of equine respiratory disease. Clin Vaccine Immunol, 20(8), 1181-1188. https://doi.org/10.1128/CVI.00069-13

Publication

ISSN: 1556-679X
NlmUniqueID: 101252125
Country: United States
Language: English
Volume: 20
Issue: 8
Pages: 1181-1188

Researcher Affiliations

Velineni, Sridhar
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.
Timoney, John F

    MeSH Terms

    • Animals
    • Antibodies, Bacterial / blood
    • Antigens, Bacterial / genetics
    • Antigens, Bacterial / immunology
    • Antigens, Bacterial / isolation & purification
    • Bacterial Proteins / genetics
    • Bacterial Proteins / immunology
    • Bacterial Proteins / isolation & purification
    • Disease Outbreaks
    • Female
    • Horse Diseases / epidemiology
    • Horse Diseases / microbiology
    • Horse Diseases / prevention & control
    • Horses
    • Male
    • Mice
    • New Caledonia
    • Opsonin Proteins / blood
    • Respiratory Tract Infections / epidemiology
    • Respiratory Tract Infections / immunology
    • Respiratory Tract Infections / microbiology
    • Respiratory Tract Infections / veterinary
    • Streptococcal Infections / epidemiology
    • Streptococcal Infections / immunology
    • Streptococcal Infections / microbiology
    • Streptococcal Infections / veterinary
    • Streptococcal Vaccines / administration & dosage
    • Streptococcal Vaccines / genetics
    • Streptococcal Vaccines / immunology
    • Streptococcus equi / genetics
    • Streptococcus equi / immunology
    • Streptococcus equi / isolation & purification

    References

    This article includes 32 references
    1. Anzai T, Walker JA, Blair MB, Chambers TM, Timoney JF. Comparison of the phenotypes of Streptococcus zooepidemicus isolated from tonsils of healthy horses and specimens obtained from foals and donkeys with pneumonia.. Am J Vet Res 2000 Feb;61(2):162-6.
      pubmed: 10685688doi: 10.2460/ajvr.2000.61.162google scholar: lookup
    2. Skjold SA, Quie PG, Fries LA, Barnham M, Cleary PP. DNA fingerprinting of Streptococcus zooepidemicus (Lancefield group C) as an aid to epidemiological study.. J Infect Dis 1987 Jun;155(6):1145-50.
      pubmed: 3572034doi: 10.1093/infdis/155.6.1145google scholar: lookup
    3. Beres SB, Sesso R, Pinto SW, Hoe NP, Porcella SF, Deleo FR, Musser JM. Genome sequence of a Lancefield group C Streptococcus zooepidemicus strain causing epidemic nephritis: new information about an old disease.. PLoS One 2008 Aug 21;3(8):e3026.
    4. Timoney JF. The pathogenic equine streptococci.. Vet Res 2004 Jul-Aug;35(4):397-409.
      pubmed: 15236673doi: 10.1051/vetres:2004025google scholar: lookup
    5. Seastone CV. HEMOLYTIC STREPTOCOCCUS LYMPHADENITIS IN GUINEA PIGS.. J Exp Med 1939 Sep 30;70(4):347-59.
      pmc: PMC2133795pubmed: 19870914doi: 10.1084/jem.70.4.347google scholar: lookup
    6. Ural O, Tuncer I, Dikici N, Aridogan B. Streptococcus zooepidemicus meningitis and bacteraemia.. Scand J Infect Dis 2003;35(3):206-7.
      pubmed: 12751721doi: 10.1080/00365540310000076google scholar: lookup
    7. Pesavento PA, Hurley KF, Bannasch MJ, Artiushin S, Timoney JF. A clonal outbreak of acute fatal hemorrhagic pneumonia in intensively housed (shelter) dogs caused by Streptococcus equi subsp. zooepidemicus.. Vet Pathol 2008 Jan;45(1):51-3.
      pubmed: 18192575doi: 10.1354/vp.45-1-51google scholar: lookup
    8. Walker JA, Timoney JF. Molecular basis of variation in protective SzP proteins of Streptococcus zooepidemicus.. Am J Vet Res 1998 Sep;59(9):1129-33.
      pubmed: 9736390
    9. Timoney JF, Walker J, Zhou M, Ding J. Cloning and sequence analysis of a protective M-like protein gene from Streptococcus equi subsp. zooepidemicus.. Infect Immun 1995 Apr;63(4):1440-5.
    10. Causey RC, Artiushin SC, Crowley IF, Weber JA, Homola AD, Kelley A, Stephenson LA, Opitz HM, Guilmain S, Timoney JF. Immunisation of the equine uterus against Streptococcus equi subspecies zooepidemicus using an intranasal attenuated Salmonella vector.. Vet J 2010 May;184(2):156-61.
      pubmed: 19482493doi: 10.1016/j.tvjl.2009.05.001google scholar: lookup
    11. Hong-Jie F, Fu-yu T, Ying M, Cheng-ping L. Virulence and antigenicity of the szp-gene deleted Streptococcus equi ssp. zooepidemicus mutant in mice.. Vaccine 2009 Jan 1;27(1):56-61.
      pubmed: 18983882doi: 10.1016/j.vaccine.2008.10.037google scholar: lookup
    12. Boschwitz JS, Timoney JF. Characterization of the antiphagocytic activity of equine fibrinogen for Streptococcus equi subsp. equi.. Microb Pathog 1994 Aug;17(2):121-9.
      pubmed: 7861956doi: 10.1006/mpat.1994.1058google scholar: lookup
    13. Sheoran AS, Sponseller BT, Holmes MA, Timoney JF. Serum and mucosal antibody isotype responses to M-like protein (SeM) of Streptococcus equi in convalescent and vaccinated horses.. Vet Immunol Immunopathol 1997 Nov;59(3-4):239-51.
      pubmed: 9477475doi: 10.1016/s0165-2427(97)00074-3google scholar: lookup
    14. Hoffman AM, Staempfli HR, Prescott JF, Viel L. Field evaluation of a commercial M-protein vaccine against Streptococcus equi infection in foals.. Am J Vet Res 1991 Apr;52(4):589-92.
      pubmed: 2053730
    15. Bazely PL. Studies with equine streptococci. 4. Cross-immunity to S. equi.. Aust. Vet. J. 18:189–194.
    16. Galán JE, Timoney JF. Immunologic and genetic comparison of Streptococcus equi isolates from the United States and Europe.. J Clin Microbiol 1988 Jun;26(6):1142-6.
    17. Timoney JF, DeNegri R, Sheoran A, Forster N. Affects of N-terminal variation in the SeM protein of Streptococcus equi on antibody and fibrinogen binding.. Vaccine 2010 Feb 10;28(6):1522-7.
      pubmed: 20005857doi: 10.1016/j.vaccine.2009.11.064google scholar: lookup
    18. 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.
    19. Timoney JF, Artiushin SC, Boschwitz JS. Comparison of the sequences and functions of Streptococcus equi M-like proteins SeM and SzPSe.. Infect Immun 1997 Sep;65(9):3600-5.
    20. LANCEFIELD RC, PERLMANN GE. Preparation and properties of type-specific M antigen isolated from a group A, type 1 hemolytic streptococcus.. J Exp Med 1952 Jul;96(1):71-82.
      pmc: PMC2136131pubmed: 14946330doi: 10.1084/jem.96.1.71google scholar: lookup
    21. Lewis MJ, Meehan M, Owen P, Woof JM. A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system.. J Biol Chem 2008 Jun 20;283(25):17615-23.
      pmc: PMC2427354pubmed: 18411272doi: 10.1074/jbc.m709844200google scholar: lookup
    22. Moore BO, Bryans JT. Type specific antigenicity of group C streptococci from disease of the horse. p 231–238 In Bryans JT, Gerber H. (ed), Equine infectious diseases II. S. Karger, Basel, Switzerland.
    23. Ben Nasr A, Wistedt A, Ringdahl U, Sjöbring U. Streptokinase activates plasminogen bound to human group C and G streptococci through M-like proteins.. Eur J Biochem 1994 Jun 1;222(2):267-76.
    24. Soedarmanto I, Pasaribu FH, Wibawan IW, Lämmler C. Identification and molecular characterization of serological group C streptococci isolated from diseased pigs and monkeys in Indonesia.. J Clin Microbiol 1996 Sep;34(9):2201-4.
    25. Bjorndottir S. Streptococcus zooepidemicus: more than just an opportunist.. J. Equine Vet. Sci. 32(Suppl):S8.
    26. Hignett SL, King WS. Streptococcal infection in the commercial horse.. Vet. J. 96:81–86.
    27. Stableforth AW, Gallaway IA. Streptococcal diseases.. In Infectious diseases of animals, diseases due to bacteria, vol 2, 589–650 Academic Press, New York, NY.
    28. Sun H, Ringdahl U, Homeister JW, Fay WP, Engleberg NC, Yang AY, Rozek LS, Wang X, Sjöbring U, Ginsburg D. Plasminogen is a critical host pathogenicity factor for group A streptococcal infection.. Science 2004 Aug 27;305(5688):1283-6.
      pubmed: 15333838doi: 10.1126/science.1101245google scholar: lookup
    29. Fulde M, Rohde M, Polok A, Preissner KT, Chhatwal GS, Bergmann S. Cooperative plasminogen recruitment to the surface of Streptococcus canis via M protein and enolase enhances bacterial survival.. mBio 2013 Mar 12;4(2):e00629-12.
      doi: 10.1128/mBio.00629-12pmc: PMC3604778pubmed: 23481605google scholar: lookup
    30. Hoffman AM, Viel L, Juniper E, Prescott JF. Clinical and endoscopic study to estimate the incidence of distal respiratory tract infection in thoroughbred foals on Ontario breeding farms.. Am J Vet Res 1993 Oct;54(10):1602-7.
      pubmed: 8250384
    31. Hoffman AM, Viel L, Prescott JF, Rosendal S, Thorsen J. Association of microbiologic flora with clinical, endoscopic, and pulmonary cytologic findings in foals with distal respiratory tract infection.. Am J Vet Res 1993 Oct;54(10):1615-22.
      pubmed: 8250386
    32. Meehan M, Lewis MJ, Byrne C, O'Hare D, Woof JM, Owen P. Localization of the equine IgG-binding domain in the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp. equi.. Microbiology (Reading) 2009 Aug;155(Pt 8):2583-2592.
      pubmed: 19423628doi: 10.1099/mic.0.028845-0google scholar: lookup

    Citations

    This article has been cited 7 times.
    1. Bergmann R, Schroedl W, Müller U, Baums CG. A distinct variant of the SzM protein of Streptococcus equi subsp. zooepidemicus recruits C1q independent of IgG binding and inhibits activation of the classical complement pathway.. Virulence 2023 Dec;14(1):2235461.
      doi: 10.1080/21505594.2023.2235461pubmed: 37450582google scholar: lookup
    2. Pan F, Zhu M, Liang Y, Yuan C, Zhang Y, Wang Y, Fan H, Waldor MK, Ma Z. Membrane vesicle delivery of a streptococcal M protein disrupts the blood-brain barrier by inducing autophagic endothelial cell death.. Proc Natl Acad Sci U S A 2023 Jun 13;120(24):e2219435120.
      doi: 10.1073/pnas.2219435120pubmed: 37276410google scholar: lookup
    3. Kuchipudi SV, Surendran Nair M, Yon M, Gontu A, Nissly RH, Barry R, Greenawalt D, Pierre T, Li L, Thirumalapura N, Tewari D, Jayarao B. A Novel Real-Time PCR Assay for the Rapid Detection of Virulent Streptococcus equi Subspecies zooepidemicus-An Emerging Pathogen of Swine.. Front Vet Sci 2021;8:604675.
      doi: 10.3389/fvets.2021.604675pubmed: 33644143google scholar: lookup
    4. D'Gama JD, Ma Z, Zhang H, Liu X, Fan H, Morris ERA, Cohen ND, Cywes-Bentley C, Pier GB, Waldor MK. A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins.. mBio 2019 Oct 22;10(5).
      doi: 10.1128/mBio.02500-19pubmed: 31641092google scholar: lookup
    5. Bergmann R, Jentsch MC, Uhlig A, Müller U, van der Linden M, Rasmussen M, Waller A, von Köckritz-Blickwede M, Baums CG. Prominent Binding of Human and Equine Fibrinogen to Streptococcus equi subsp. zooepidemicus Is Mediated by Specific SzM Types and Is a Distinct Phenotype of Zoonotic Isolates.. Infect Immun 2019 Dec 17;88(1).
      doi: 10.1128/IAI.00559-19pubmed: 31636136google scholar: lookup
    6. Watson JR, Leber A, Velineni S, Timoney JF, Ardura MI. Recurrent Streptococcus equi subsp. zooepidemicus Bacteremia in an Infant.. J Clin Microbiol 2015 Sep;53(9):3096-9.
      doi: 10.1128/JCM.01306-15pubmed: 26179301google scholar: lookup
    7. Velineni S, Timoney JF, Russell K, Hamlen HJ, Pesavento P, Fortney WD, Crawford PC. Clones of Streptococcus zooepidemicus from outbreaks of hemorrhagic canine pneumonia and associated immune responses.. Clin Vaccine Immunol 2014 Sep;21(9):1246-52.
      doi: 10.1128/CVI.00222-14pubmed: 24990905google scholar: lookup