Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Sep;65(9):3828–3833. doi: 10.1128/iai.65.9.3828-3833.1997

Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced by a T1 strain of Streptococcus pyogenes.

Y Kamezawa 1, T Nakahara 1, S Nakano 1, Y Abe 1, J Nozaki-Renard 1, T Isono 1
PMCID: PMC175546  PMID: 9284159

Abstract

Streptococcus pyogenes T1 was previously found to produce an acidic mitogenic exotoxin, designated A beta, antigenically distinct from erythrogenic toxin type A (ETA) of strains T1 and NY5. Following chemical analysis and biological characterization, we have renamed this toxin streptococcal mitogenic exotoxin Z (SMEZ). Physicochemical separation of SMEZ from ETA was successfully performed on a hydrophobic chromatograph. The isoelectric point was pH 5.3, and the molecular size was estimated to be 28 kDa. These values were similar to those of ETA, but the amino acid composition and the NH2-terminal sequence of SMEZ were distinct from those of any mitogenic exotoxins hitherto described. Its mitogenic activity was found to be more potent than that of ETA in rabbit lymphocyte cultures. A specific antiserum raised against SMEZ did not cross-react with ETA, ETB, or ETC in the neutralization tests of mitogenic and erythrogenic activities. Its superantigenic nature was evident from the reverse transcriptase PCR findings of the T-cell receptor Vbeta profiles of rabbit lymphocytes stimulated in vitro. The Vbeta 8 subfamily was unique to SMEZ, while the Vbeta 2 and 6 subfamilies were found to be common among lymphocytes stimulated with ETA, ETB, ETC, or SMEZ. The results from this study provide an additional example of the diversity that exists among mitogenic or superantigenic exotoxins of streptococcal origin.

Full Text

The Full Text of this article is available as a PDF (321.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe J., Forrester J., Nakahara T., Lafferty J. A., Kotzin B. L., Leung D. Y. Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B. J Immunol. 1991 Jun 1;146(11):3747–3750. [PubMed] [Google Scholar]
  2. Abe Y., Nakano S., Nakahara T., Kamezawa Y., Kato I., Ushijima H., Yoshino K., Ito S., Noma S., Okitsu S. Detection of serum antibody by the antimitogen assay against streptococcal erythrogenic toxins. Age distribution in children and the relation to Kawasaki disease. Pediatr Res. 1990 Jan;27(1):11–15. doi: 10.1203/00006450-199001000-00003. [DOI] [PubMed] [Google Scholar]
  3. Barsumian E. L., Cunningham C. M., Schlievert P. M., Watson D. W. Heterogeneity of group A streptococcal pyrogenic exotoxin type B. Infect Immun. 1978 May;20(2):512–518. doi: 10.1128/iai.20.2.512-518.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bohach G. A., Hauser A. R., Schlievert P. M. Cloning of the gene, speB, for streptococcal pyrogenic exotoxin type B in Escherichia coli. Infect Immun. 1988 Jun;56(6):1665–1667. doi: 10.1128/iai.56.6.1665-1667.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braun M. A., Gerlach D., Hartwig U. F., Ozegowski J. H., Romagné F., Carrel S., Köhler W., Fleischer B. Stimulation of human T cells by streptococcal "superantigen" erythrogenic toxins (scarlet fever toxins). J Immunol. 1993 Mar 15;150(6):2457–2466. [PubMed] [Google Scholar]
  6. Cavaillon J. M., Leclerc C., Alouf J. E. Polyclonal antibody-forming cell activation and immunomodulation of the in vitro immune response induced by streptococcal extracellular products. Cell Immunol. 1983 Feb 15;76(1):200–206. doi: 10.1016/0008-8749(83)90362-3. [DOI] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Cunningham C. M., Barsumian E. L., Watson D. W. Further purification of group A streptococcal pyrogenic exotoxin and characterization of the purified toxin. Infect Immun. 1976 Sep;14(3):767–775. doi: 10.1128/iai.14.3.767-775.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fast D. J., Schlievert P. M., Nelson R. D. Toxic shock syndrome-associated staphylococcal and streptococcal pyrogenic toxins are potent inducers of tumor necrosis factor production. Infect Immun. 1989 Jan;57(1):291–294. doi: 10.1128/iai.57.1.291-294.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gerlach D., Alouf H., Morávek L., Pavlik M., Köhler W. The characterization of two new low molecular weight proteins (LMPs) from Streptococcus pyogenes. Zentralbl Bakteriol. 1992 Jun;277(1):1–9. doi: 10.1016/s0934-8840(11)80864-9. [DOI] [PubMed] [Google Scholar]
  11. Gerlach D., Günther E., Köhler W., Vettermann S., Fleischer B., Schmidt K. H. Isolation and characterization of a mitogen characteristic of group A streptococci (Streptococcus pyogenes). Zentralbl Bakteriol. 1995 Jan;282(1):67–82. [PubMed] [Google Scholar]
  12. Gerlach D., Knöll H., Köhler W., Ozegowski J. H., Hríbalova V. Isolation and characterization of erythrogenic toxins. V. Communication: identity of erythrogenic toxin type B and streptococcal proteinase precursor. Zentralbl Bakteriol Mikrobiol Hyg A. 1983 Sep;255(2-3):221–233. [PubMed] [Google Scholar]
  13. Gerlach D., Köhler W., Knöll H., Moravek L., Weeks C. R., Ferretti J. J. Purification and characterization of Streptococcus pyogenes erythrogenic toxin type A produced by a cloned gene in Streptococcus sanguis. Zentralbl Bakteriol Mikrobiol Hyg A. 1987 Oct;266(3-4):347–358. doi: 10.1016/s0176-6724(87)80215-8. [DOI] [PubMed] [Google Scholar]
  14. Goshorn S. C., Schlievert P. M. Nucleotide sequence of streptococcal pyrogenic exotoxin type C. Infect Immun. 1988 Sep;56(9):2518–2520. doi: 10.1128/iai.56.9.2518-2520.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gray E. D. Purification and properties of an extracellular blastogen produced by group A streptococci. J Exp Med. 1979 Jun 1;149(6):1438–1449. doi: 10.1084/jem.149.6.1438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hackett S. P., Stevens D. L. Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis. J Infect Dis. 1993 Jul;168(1):232–235. doi: 10.1093/infdis/168.1.232. [DOI] [PubMed] [Google Scholar]
  17. Hauser A. R., Schlievert P. M. Nucleotide sequence of the streptococcal pyrogenic exotoxin type B gene and relationship between the toxin and the streptococcal proteinase precursor. J Bacteriol. 1990 Aug;172(8):4536–4542. doi: 10.1128/jb.172.8.4536-4542.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Isono T., Isegawa Y., Seto A. Analysis of T cell receptor V beta expression in rabbit T lymphocytes induced to proliferate by an HTLV-I-transformed leukemogenic T cell line. J Cancer Res Clin Oncol. 1996;122(8):458–464. doi: 10.1007/BF01187157. [DOI] [PubMed] [Google Scholar]
  19. Iwasaki M., Igarashi H., Hinuma Y., Yutsudo T. Cloning, characterization and overexpression of a Streptococcus pyogenes gene encoding a new type of mitogenic factor. FEBS Lett. 1993 Sep 27;331(1-2):187–192. doi: 10.1016/0014-5793(93)80323-m. [DOI] [PubMed] [Google Scholar]
  20. Kamezawa Y., Nakahara T. Purification and characterization of streptococcal erythrogenic toxin type A produced by Streptococcus pyogenes strain NY-5 cultured in the synthetic medium NCTC-135. Comparison with the dialyzed medium (TP medium)-derived toxin. Microbiol Immunol. 1989;33(3):183–194. doi: 10.1111/j.1348-0421.1989.tb01512.x. [DOI] [PubMed] [Google Scholar]
  21. König B., Köller M., Prevost G., Piemont Y., Alouf J. E., Schreiner A., König W. Activation of human effector cells by different bacterial toxins (leukocidin, alveolysin, and erythrogenic toxin A): generation of interleukin-8. Infect Immun. 1994 Nov;62(11):4831–4837. doi: 10.1128/iai.62.11.4831-4837.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Mollick J. A., Miller G. G., Musser J. M., Cook R. G., Grossman D., Rich R. R. A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C. J Clin Invest. 1993 Aug;92(2):710–719. doi: 10.1172/JCI116641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Müller-Alouf H., Alouf J. E., Gerlach D., Ozegowski J. H., Fitting C., Cavaillon J. M. Comparative study of cytokine release by human peripheral blood mononuclear cells stimulated with Streptococcus pyogenes superantigenic erythrogenic toxins, heat-killed streptococci, and lipopolysaccharide. Infect Immun. 1994 Nov;62(11):4915–4921. doi: 10.1128/iai.62.11.4915-4921.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nelson K., Schlievert P. M., Selander R. K., Musser J. M. Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes. J Exp Med. 1991 Nov 1;174(5):1271–1274. doi: 10.1084/jem.174.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Norrby-Teglund A., Newton D., Kotb M., Holm S. E., Norgren M. Superantigenic properties of the group A streptococcal exotoxin SpeF (MF). Infect Immun. 1994 Dec;62(12):5227–5233. doi: 10.1128/iai.62.12.5227-5233.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Norrby-Teglund A., Norgren M., Holm S. E., 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):3731–3738. doi: 10.1128/iai.62.9.3731-3738.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ozegowski J. H., Knöll H., Gerlach D., Köhler W. Isolierung und Charakterisierung von erythrogenen Toxinen. VII. Untersuchung des von Streptococcus pyogenes gebildeten erythrogenen Toxins Typ C. Zentralbl Bakteriol Mikrobiol Hyg A. 1984 May;257(1):38–50. [PubMed] [Google Scholar]
  29. Schlievert P. M., Bettin K. M., Watson D. W. Purification and characterization of group A streptococcal pyrogenic exotoxin type C. Infect Immun. 1977 May;16(2):673–679. doi: 10.1128/iai.16.2.673-679.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schlievert P. M., Gray E. D. Group A streptococcal pyrogenic exotoxin (scarlet fever toxin) type A and blastogen A are the same protein. Infect Immun. 1989 Jun;57(6):1865–1867. doi: 10.1128/iai.57.6.1865-1867.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tomai M. A., Schlievert P. M., Kotb M. Distinct T-cell receptor V beta gene usage by human T lymphocytes stimulated with the streptococcal pyrogenic exotoxins and pep M5 protein. Infect Immun. 1992 Feb;60(2):701–705. doi: 10.1128/iai.60.2.701-705.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weeks C. R., Ferretti J. J. Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from Streptococcus pyogenes bacteriophage T12. Infect Immun. 1986 Apr;52(1):144–150. doi: 10.1128/iai.52.1.144-150.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yutsudo T., Murai H., Gonzalez J., Takao T., Shimonishi Y., Takeda Y., Igarashi H., Hinuma Y. A new type of mitogenic factor produced by Streptococcus pyogenes. FEBS Lett. 1992 Aug 10;308(1):30–34. doi: 10.1016/0014-5793(92)81043-l. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES