Structure, Function and Role in Disease of Pneumolysin, The Thiol-Activated Toxin of Streptococcus Pneumoniae

  • G. J. Boulnois
  • T. Mitchell
  • K. Saunders
  • X. Mendez
  • P. Andrew
Part of the Federation of European Microbiological Societies Symposium Series book series (FEMS, volume 51)


Pneumolysin, the thiol-activated toxin of Streptococcus pneumoniae is one of a family of toxins produced by four different genera of Gram positive bacteria (1). This family of toxins share a variety of physical and biological properties and exert their effects via damage to eukaryotic membranes (2). A striking feature of this family is their pronounced immunological cross-reactivity such that sera raised against one member of this family generally reacts with and often neutralizes and precipitates heterologous toxin (1). They are termed thiol-activated since they are inactivated upon oxidation and treatment with reducing agents restores full activity (1). This was thought to reflect the formation and breakage of intra-molecular disulfide bridges, a process which induces conformational changes in the protein which are reflected in their ability to interact with membranes (3). As well as mediating such changes, a single sulphydryl was postulated to be essential for activity (4). However, the role this essential cysteine plays in toxin activity is unclear. The thiol-activated toxins are thought to utilize cholesterol as receptor since their cytolytic activity is only manifest on cells which have cholesterol as part of their membranes and since free cholesterol is a potent inhibitor of cytolytic activity (1, 2). It has been postulated that this essential sulphydryl group may mediate (or is involved in) the interaction of the toxin and cholesterol (6). It should be noted that cholesterol has not been shown conclusively to act as the receptor for these toxins.


Hemolytic Activity Cytolytic Activity Pneumococcal Infection Receptor Binding Domain Single Cysteine 
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  1. 1.
    Smyth, C.J. and J.L. Duncan. 1978. In Bacterial Toxins and Cell Membranes. J. Jeljaszewice and T. Wadstrom, Eds. pp. 129–183. Academic Press, London.Google Scholar
  2. 2.
    Bhakdi, S. and J. Tranum-Jensen. 1986. Microb. Pathogen. 1:5–14.CrossRefGoogle Scholar
  3. 3.
    Alouf, J.E. 1980. Pharmac. Ther. 11:661–717.CrossRefGoogle Scholar
  4. 4.
    Geoffrey, G., A.-M. Gilles and J.E. Alouf. 1981. Biochem. Biophys. Acta 99:781–788.Google Scholar
  5. 5.
    Mengaud, J., M.-F. Vincente. J. Chenevert, J.M. Pereira, C. Geoffrey, B. Gicquell-Sanzey, F. Baquero, J.-C. Perez-Diaz and P. Cossart. 1988. Infect. Immun. 556:766–771.Google Scholar
  6. 6.
    Duncan, J.L. and R. Schlägel. 1975. J. Cell. Biol. 67:160–173.PubMedCrossRefGoogle Scholar
  7. 7.
    Bhakdi, S., J. Tranum-Jensen and A. Szieysleit. 1985. Infect.Immun. 47:52–60.PubMedGoogle Scholar
  8. 8.
    Bhakdi, S. and J. Tranum-Jensen. 1987. Rev.Physiol.-Biochem.Pharmacol. 107:147–227.PubMedCrossRefGoogle Scholar
  9. 9.
    Paton, J.C. and A. Ferrante. 1983. Infect.Immun. 41:1212–1216.PubMedGoogle Scholar
  10. 10.
    Ferrante, A., B. Rowan-Kelly and J.C. Paton. 1984. Infect.Immun. 46: 585–589.PubMedGoogle Scholar
  11. 11.
    Paton, J.C., B. Rowan-Kelly and A. Ferrante. 1984. Infect.Immun. 43, 1085–1087.PubMedGoogle Scholar
  12. 12.
    Walker, J.A., R.L. Allen, P. Falmagne, M.K Johnson and G.J. Boulnois. 1987. Infect.Immun. 55:1184–1189.PubMedGoogle Scholar
  13. 13.
    Mitchell, T.J., J.A. Walker, F.K. Saunders, P.W. Andrew and G.J. Boulnois. 1989. Biochem.Biophys.Acta. 1007, 67–72.PubMedGoogle Scholar
  14. 14.
    Kehoe, M.A., L. Miller, J.A. Walker and G.J. Boulnois. 1987. Infect.Immun. 55:3228–3232.PubMedGoogle Scholar
  15. 15.
    Tweten, R. 1988. Infect.Immun. 56: 3235–3240.PubMedGoogle Scholar
  16. 16.
    Johnson, M.K. 1977. F.E.M.S. Microbiol. Lett. 2:243–245.CrossRefGoogle Scholar
  17. 17.
    Saunders, F.K., T.J. Mitchell, J.A. Walker, P.W. Andrew and G.J. Boulnois. 1989. Infect.Immun. In Press.Google Scholar
  18. 18.
    Edwards, K.M., C. Mold, R. F. List, H. Gewürz. 1980. Clin.Res. 28:735A.Google Scholar
  19. 19.
    Horowitz, J., J.E. Volonakis and D.E. Briles. 1987. J.Immunol. 138:2598–2603.PubMedGoogle Scholar
  20. 20.
    Mold, C., S. Nakayama, T.J. Holzer, H. Gewürz and T.W. Du Cols. 1981. J.Exp.Med. 154: 1705–1708.CrossRefGoogle Scholar
  21. 21.
    Yother, J., J.E. Volanakis and D.E. Briles. 1982. J.Immunol. 128, 2374–2376.PubMedGoogle Scholar
  22. 22.
    Kaiin, M., K. Kanderski, M. Granstrom and R. Mollby. 1987. J.Clin.Microbiol. 25:226–229.Google Scholar
  23. 23.
    Paton, J.C., R.A. Lock and D.J. Hansman. 1983. Infect.Immun. 40:548–552.PubMedGoogle Scholar
  24. 24.
    Steinfort, C., R. Wilson, T. Mitchell, C. Feldman, A. Rutman, H. Todd, D. Sykes, J.Walker, K. Saunders, P.W. Andrew, G.J. Boulnois and P.J. Cole. 1989. Infeet.Immun. In Press.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • G. J. Boulnois
    • 1
  • T. Mitchell
    • 1
  • K. Saunders
    • 1
  • X. Mendez
    • 1
  • P. Andrew
    • 1
  1. 1.Department of MicrobiologyUniversity of LeicesterLeicesterUK

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