Advertisement

Medical Microbiology and Immunology

, Volume 184, Issue 2, pp 53–61 | Cite as

The epidermolytic (exfoliative) toxins of Staphylococcus aureus

  • Christopher J. Bailey
  • Brian P. Lockhart
  • Maria B. Redpath
  • Thomas P. Smith
Review

Abstract

Two epidermolytic toxins, produced by different strains of Staphylococcus aureus, split human skin at a site in the upper epidermis. Clinical effects are most common in infants, but adults are susceptible. Epidermolysis may also be observed in the mouse, in vivo and in vitro, and in a few other mammals. Recent in vitro experiments have demonstrated an inhibition by chelators and point to metal-ion, possibly Ca2+, involvement. The epidermolysis effect is insensitive to a wide range of other metabolic inhibitors. The toxin amino acid sequences are similar to that of staphylococcal proteinase, and new experiments by chemical modification and site-directed mutagenesis have shown that toxicity depends on ‘active serine’ residues of a catalytic triad similar to that found in serine proteases. Furthermore the toxins possess esterolytic activity, also dependent on the ‘active serine’ sites. However, the toxins have low or undetectable activity towards a range of peptide or protein substrates. In histological and related studies, the toxins bound selectively to an intracellular skin protein, profilaggrin, but there was no evidence that the toxin can enter intact epidermal cells. Therefore, although the circumstantial evidence that the toxins act by proteolysis is convincing, a specific skin proteolytic substrate for the toxin has not been identified.

Key words

Staphylococcus aureus Epidermis Toxin Chelator Active serine Profilaggrin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Arbuthnott JP, Kent J, Lyell A, Gemmell CG (1971) Toxic Epidermal necrolysis produced by an extracellular product of Staphylococcus aureus. Br J Dermatol 85:145–149Google Scholar
  2. 2.
    Arbuthnott JP, Kent J, Noble WC (1973) The response of hairless mice to Staphylococcal epidermolytic toxin. Br J Dermatol 88:481–485Google Scholar
  3. 3.
    Baker DH, Dimond RL, Wuepper KD (1978) The epidermolytic toxin of S. aureus. Its failure to bind to cells and its detection in blister fluids of patients with Bullous impetigo. J Invest Dermatol 71:274–275Google Scholar
  4. 4.
    Bailey CJ, Redpath MB (1992) The esterolytic activity of epidermolytic toxins. Biochem J 284:177–180Google Scholar
  5. 5.
    Bailey CJ, Smith TP (1990) The reactive serine of epidermolytic toxin A. Biochem J 269:535–537Google Scholar
  6. 6.
    Bailey CJ, de Azavedo J, Arbuthnott JP (1980) A comparative study of two serotypes of epidermolytic toxin from Staphylococcus aureus. Biochem Biophys Acta 624:111–120Google Scholar
  7. 7.
    Bailey CJ, Martin SR, Bayley PM (1982) A circular dichroism study of epidermolytic toxins A & B from Staphylococcus aureus. Biochem J 203:775–778Google Scholar
  8. 8.
    Bhakdi S, Grimminger F, Suttorp N, Walmrath D, Seeger W (1994) Proteinaceous bacterial toxins and pathogenesis of sepsin syndrome and septic shock: the unknown connection. Med Microbiol Immunol 180:273–278Google Scholar
  9. 9.
    Buxton RS, et al. (1993) Nomenclature of the desmosomal cadherins. J Cell Biol 121:481–483Google Scholar
  10. 10.
    Chen F-S, Melish ME (1982) Demonstration of staphylococcal epidermolytic toxin receptors in human and murine skin. Fed Proc 41:139Google Scholar
  11. 11.
    Dancer SJ, Garratt R, Saldanha J, Jhoti H, Evans R (1990) The epidermolytic toxins are serine proteases. FEBS Lett 268:129–132Google Scholar
  12. 12.
    Dancer SJ, Poston SM, East J, Simmons MA, Noble WC (1990) An outbreak of pemphigous neonatorum. J Infect 20:73–82Google Scholar
  13. 13.
    Dave J, Reith S, Nash JQ, Marples RR, Dulake C (1994) A double outbreak of exfoliative toxin-producing strains of Staphylococcus aureus in a maternity unit. Epidemiol Infect 112:103–114Google Scholar
  14. 14.
    De Azavedo JCS, Arbuthnott JP (1988) Assays for epidermolytic toxin of Staphylococcus aureus. Method Enzymol 165:333–338Google Scholar
  15. 15.
    Dimond RL, Wuepper KD (1976) Purification and characterisation of a staphylococcal epidermolytic toxin. Infect Immun 13:627–633Google Scholar
  16. 16.
    Drapeau GR (1978) The primary structure of staphylococcal protease. Can J Biochem 56:534–544Google Scholar
  17. 17.
    Elias PM, Fritsch P, Tappeiner G, Mittermayer H, Wolff K (1974) Experimental Staphylococcal toxic epidermal necrolysis (TEN) in adult humans and mice. J Lab Clin Med 84:414–424Google Scholar
  18. 18.
    Elias PM, Fritsch P, Mittermeyer H (1976) Staphyococcal toxic epidermal necrolysis: species and tissue susceptibility and resistance. J Invest Dermatol 66:80–89Google Scholar
  19. 19.
    Elias PM, Fritsch P, Epstein EH (1977) Staphylococcal scalded skin syndrome. Arch Dermatol 113:207–219Google Scholar
  20. 20.
    Elsner P, Hartman AA, Lenz W, Brandis H (1985) Screening of clinical S aureus isolates for the production of exfoliative toxin. Zentrabl Bakteriol Mikrobiol Hyg 260:216–220Google Scholar
  21. 21.
    Fleischer B, Bailey CJ (1992) Recombinant epidermolytic (exfoliative) toxin A of Staphylococcus aureus is not a superantigen. Med Microbiol Immunol 180:273–278Google Scholar
  22. 22.
    Freer J, Arbuthnott JP (1983) Toxins of Staphylococcus aureus. Pharmacol Therapeut 19:55–106Google Scholar
  23. 23.
    Freinkel RK, Traczyk TN (1981) A method for partial purification of lamellar granules from fetal rat epidermis. J Invest Dermatol 77:478–482Google Scholar
  24. 24.
    Fritsch P, Elias PM, Varga J (1976) The fate of Staphylococcal exfoliatin in newborn and adult mice. Br J Dermatol 95:275–284Google Scholar
  25. 25.
    Fritsch PO, Kaasaver G, Elias PM (1979) Action of staphylococcal epidermolysin: further observations on its species specificity. Archs Dermatol Res 264:287–291Google Scholar
  26. 26.
    Gentilhomme E, Faure M, Binder P, Thivolet J (1990) Action of staphylococcal exfoliative toxins on epidermal cell cultures and organotypic skin. J Dermatol 17:526–532Google Scholar
  27. 27.
    Gray SG, Kehoe M (1984)Primary structure of the a-toxin gene from Staphylococcus aureus. Infect Immun 46:615–618Google Scholar
  28. 28.
    Grayson S, Johnson-Winegar AG, Wintroub BU, Isserott RR, Epstein EH, Elias PM (1984) Lamellar body-enriched fractions from neonatal mice:preparative techniques and partial characterisation. J Invest Dermatol 85:289–299Google Scholar
  29. 29.
    Herman A, Kappler JM, Marrack P, Pullen AM (1990) Superantigens:mechanism of T cell stimulation and role in immune response. Annu Rev Immunol 9:745–772Google Scholar
  30. 30.
    Inaoki M (1990) Experimental studies on the mechanism of action of Staphylococcal epidermolytic toxin A utilizing recombinant toxin. Nippon Hituka Gakkai Zasshi 100:1405–1414Google Scholar
  31. 31.
    Jackson MP, Iandolo JJ (1986) Sequence of the exfoliative toxin B gene of Staphylococcus aureus. J Bacteriol 167:574–580Google Scholar
  32. 32.
    Johnson AD, Metzgen JF, Spero L (1975) Productive purification and Chemical characterisation of Staphylococcus aureus exfoliative toxin. Infect Immun 12:1206–1210Google Scholar
  33. 33.
    Johnson AD, Spero L, Cades JS, De Cicco BT (1979) Purification and characterisation of different types of exfoliative toxin from Staphylococcus aureus. Infect Immun 24:679–684Google Scholar
  34. 34.
    Kaplan MH, Chmel H, Hsieh HC, Stephens A, Brinsko V (1986) Importance of exfoliatin A production by Staphylococcus aureus strains isolated from clustered epidemics of neonatal pustulosis. J Clin Microbiol 23:83–91Google Scholar
  35. 35.
    Kapral FA, Miller MM (1971) Product of Staphylococcus aureus responsible for the scalded-skin syndrome. Infect Immun 4:541–545Google Scholar
  36. 36.
    Kondo I, Sakurai S, Sari Y (1976) Staphylococcal exfoliation A and B. In: Jeljaszewicz J (ed) Staphylococci and staphylococcal diseases. Gustav Fischer, Stuttgart, pp 489–498Google Scholar
  37. 37.
    Lee CY, Schmidt JJ, Johnson-Winegar AD, Spero L, Iandolo JJ (1987) Sequence determination and comparison of the exfoliative toxin A and toxin B genes from Staphylococcus aureus. J Bacteriol 169:3904–3909Google Scholar
  38. 38.
    Lillibridge CB, Melish ME, Glasgow LA (1972) Site of action of exfoliative toxin in the staphylococcal scalded-skin syndrome. Pediatrics 50:728–738Google Scholar
  39. 39.
    Lockhart BP, Bailey CJ (1993) ELISA estimation of the binding of epidermolytic toxin to neonatal mouse skin. Toxicon 31:569–576Google Scholar
  40. 40.
    Lockhart BP, Smith TP, Bailey CJ (1991) Immunofluorescence localization of the epidermolytic toxin target in mouse epidermal cells and tissue. Histochem J 23:385–391Google Scholar
  41. 41.
    Lyell A (1979) Toxic epidermal necrolysis (the scalded skin syndrome: a reappraisal). Br J Dermatol 100:69–86Google Scholar
  42. 42.
    McCallum HM (1972) Action of staphylococcal epidermolytic toxin on mouse skin in organ culture. Br J Dermatol 86 [Suppl 8]:40–41Google Scholar
  43. 43.
    McLay ALC, Arbuthnott JP, Lyell A (1975) Action of Staphylococcal epidermolytic toxin on mouse skin: an electron microscopic study. J Invest Derm 65:423–428Google Scholar
  44. 44.
    Melish ME, Glasgow LA (1970) The staphylococcal scalded skin syndrome: Development of an experimental model. N Engl J Med 282:1114–1119Google Scholar
  45. 45.
    Melish ME, Glasgow LA (1971) Staphylococcal scalded skin syndrome: the expanded clinical syndrome. J Pediatr 78:958–967Google Scholar
  46. 46.
    Melish ME, Chen FS, Sprouse S, Stuckey M, Murata MS (1981) Epidermolytic toxin in Staphylococcal infection: toxin levels and host response. In: Jeljaszewicz J (ed) Staphylococci and staphylococcal infections. Fischer, Stuttgart, pp 287–298Google Scholar
  47. 47.
    Nishioka K, Katayama I, Sano S (1981) Possible binding of epidermolytic toxin to a subcellular fraction of the epidermis. J Dermatol 8:7–12Google Scholar
  48. 48.
    Opal SM, Johnston-Winegar AD, Cross AS (1988) Staphylococcal scalded skin syndrome in two immunocompetent adults caused by exfoliation B-producing Staphylococcus aureus. J Clin Microbiiol 26:1283–1286Google Scholar
  49. 49.
    O'Toole P, Foster TJ (1986) Molecular cloning and expression of the epidermolytic toxin A gene of Staphylococcus aureus. Microbial Pathogenesis 1:583–594Google Scholar
  50. 50.
    O'Toole PW, Foster TJ (1987) Nucleotide sequence of the Epidermolytic Toxin A gene of Staphylococcus aureus. J Bacteriol 169:3910–3915Google Scholar
  51. 51.
    Prévost G, Rifai S, Chaix ML, Piédmont Y (1991) Functional evidence that the Ser-195 residue of staphylococcal exfoliative toxin A is essential for biological activity. Infect Immun 59:3337–3339Google Scholar
  52. 52.
    Prévost G, Rifai S, Chaix ML, Meyer S, Piédmont Y (1992) Is the His72, Asp120, Ser195 triad constitutive of the catalytic site of staphylococcal exfoliative toxin A? In: Witholt B et al. (eds) Bacterial protein toxins. Fischer, Stuttgart, pp 488–489Google Scholar
  53. 53.
    Redpath MB, Foster TJ, Bailey CJ (1991) The role of the serine protease active site in the mode of action of epidermolytic toxin of Staphylococcus aureus. FEMS Microbiol Lett 81:151–156Google Scholar
  54. 54.
    Sakurai S, Kondo I (1978) Characterisation of staphylococcal exfoliatin A as a metallotoxin with special reference to determination of the contained metal by radioactivation analysis. Jpn J Med Sci Biol 31:208–211Google Scholar
  55. 55.
    Sakurai S, Suzaki H, Kondo I (1988) DNA sequencing of the eta gene coding for staphylococcal exfoliatin toxin serotype A. J Gen Microbiol 134:711–717Google Scholar
  56. 56.
    Sato H, Kuramato M, Tanabe T, Saito H (1991) Susceptibility of various animals and cultured cells to exfoliative toxin produced by Staphylococcus hyicus subsp.-hyicus. Vet Microbiol 28:157–169Google Scholar
  57. 57.
    Sheehan BJ, Foster TJ, Dorman CJ, Park S, Stewart GSAB (1992) Osmotic and growth-phase dependent regulation of the etagene of Staphylococcus aureus: a role for DNA supercoiling. Mol Gen Genet 232:49–57Google Scholar
  58. 58.
    Skerrow CJ (1980) The experimental production of high-level intraepidermal splits. Br J Dermatol 102:75–83Google Scholar
  59. 59.
    Smith TP, Bailey CJ (1986) Epidermolytic toxin from Staphylococcus aureus binds to filaggrins. FEBS Lett 194:309–312Google Scholar
  60. 60.
    Smith TP, Bailey CJ (1990) Activity requirements of epidermolytic toxin from Staphylococcus aureus studied by an in vitro assay. Toxicon 28:675–683Google Scholar
  61. 61.
    Smith TP, John DA, Bailey CJ (1987) The binding of epidermolytic toxin from Staphylococcus aureus to mouse epidermal tissue. Histochem J 19:137–149Google Scholar
  62. 62.
    Smith TP, John DA, Bailey CJ (1989) Epidermolytic toxin binds to components in the epidermis of a resistant species. Eur J Cell Biol 49:341–149Google Scholar
  63. 63.
    Stanley JR (1989) Pemphigus and Pemphigoid as paradigms of organ-specific autoantibody-mediated diseases. J Clin Invest 83:1443–1448Google Scholar
  64. 64.
    Stephen J, Pietrowski RA (1986) Bacterial toxins. American Society for Microbiology, Washington, pp 8–10Google Scholar
  65. 65.
    Tanabe T, Sato H, Kuramato M, Saito H (1993) Purification of exfoliative toxin produced by Staphylococcus hyicus and its antigenicity. Infect Immun 61:2973–2977Google Scholar
  66. 66.
    Uhlen M, guss B, Nilsson B, Grantenbeck S, Philipson L, Lindberg M (1984) Complete sequence of the staphylococcal gene encoding protein A. J Biol Chem 259:1695–1702Google Scholar
  67. 67.
    Wuepper KD, Dimond RL, Knutson DD (1975) Studies in the mechanism of epidermal injury on Staphylococcal epidermolytic toxin. J Invest Dermatol 65:191–200Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Christopher J. Bailey
    • 1
  • Brian P. Lockhart
    • 1
  • Maria B. Redpath
    • 1
  • Thomas P. Smith
    • 1
  1. 1.Department of BiochemistryTrinity CollegeDublinIreland

Personalised recommendations