Skip to main content
SpringerLink
Log in

Ultrastructural changes in HEp-2 cells treated with staphylococcal α-toxin

  • Original Contributions
  • Published:
Ricerca in clinica e in laboratorio

Summary

The effect of highly purified staphylococcal α-toxin on HEp-2 neoplastic cells growing in culture was studied by electron microscopy. In addition to some nuclear modifications, the most significant morphological changes were in mitochondrial structure. α-toxin seems to induce a defined sequence of changes in mitochondrial configuration which can be summarized as an earlier phase of ‘condensation’ of mitochondrial structure and a later phase of mitochondrial swelling with an intermediate ‘transitional’ configuration. The significance of these findings is discussed in the light of the present state of knowledge of the biological characteristics of staphylococcal α-toxin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IU:

International Units

MHD:

Minimal Haemolytic Dose

References

  1. Bernheimer A. W., Avigad L. S., Grushoff P.: Lytic Effects of Staphylococcal α-Toxin and δ-Haemolysin — J. Bact.96, 487, 1968.

    Article  PubMed  CAS  Google Scholar 

  2. Bernheimer A. W., Schwartz L. L.: Lysosomal Disruption by Bacterial Toxins — J. Bact.87, 1100, 1964.

    PubMed  CAS  Google Scholar 

  3. Buckelew A. R., Colacicco G.: Lipid Monolayers. Interaction with Staphylococcal α-Toxin — Biochim. biophys. Acta (Amst.)233, 7, 1971.

    Article  CAS  Google Scholar 

  4. Buffa P., Guarriero-Bobyleva V., Muscatello U., Pasquali-Ronchetti I.: Conformational Changes of Mitochondria Associated with Uncoupling of Oxidative Phosphorylationin Vivo andin Vitro — Nature (Lond.)226, 272, 1970.

    Article  CAS  Google Scholar 

  5. Cassidy P., Six H. R., Harshman S.: Biological Properties of Staphylococcal α-Toxin — Biochim. biophys. Acta (Amst.)332, 413, 1974.

    Article  CAS  Google Scholar 

  6. Crocker B. P., Jr.,Saladino A. J., Trump B. F.: Ion Movements in Cell Injury: Relationship between Energy Metabolism and the Pathogenesis of Lethal Injury in the Toad Bladder — Amer. J. Path.59, 247, 1970.

    Google Scholar 

  7. Deamer D. W., Utsumi K., Packer L.: Oscillatory States of Mitochondria. III. Ultrastructure of Trapped Configurational States — Arch. Biochem.121, 641, 1967.

    Article  PubMed  CAS  Google Scholar 

  8. Freer J. H., Arbuthnott J. P., Bernheimer A. W.: Interaction of Staphylococcal α-Toxin with Artificial and Natural Membranes — J. Bact.95, 1153, 1968.

    PubMed  CAS  Google Scholar 

  9. Freer J. H., Arbuthnott J. P., Billcliffe B.: Effects of Staphylococcal α-Toxin on the Structure of Erythrocyte Membranes: A Biochemical and Freeze-Etching Study — J. gen. Microbiol.75, 321, 1973.

    PubMed  CAS  Google Scholar 

  10. Gabliks S., Solotorovsky M.: Cell Cultures Reactivity to Diphtheria,Staphylococcus, Tetanus and E.coli Toxins — J. Immunol.88, 505, 1962.

    PubMed  CAS  Google Scholar 

  11. Galanti B., Paradisi F., Mancini A., Giusti G.: An Early Effect ofStaphylococcus α-Toxin on Cells Growing in Culture: ATP Levels in Normal and Intoxicated Cells — Path. et Microbiol. (Basel)32, 277, 1968.

    CAS  Google Scholar 

  12. Greenwalt J. W., Rossi C. S., Lehninger A. L.: Effect of Active Accumulation of Calcium and Phosphate Ions on the Structure of Rat Liver Mitochondria — J. Cell Biol.23, 21, 1964.

    Article  Google Scholar 

  13. Hackenbrock C. R.: Ultrastructural Basis for Metabolically Linked Mechanical Activity in Mitochondria. I. Reversible Ultrastructural Changes with Change in Metabolic Steady State in Isolated Liver Mitochondria — J. Cell Biol.30, 269, 1966.

    Article  PubMed  CAS  Google Scholar 

  14. Hackenbrock C. R.: Ultrastructural Basis for Metabolically Linked Mechanical Activity in Mitochondria. II. Electron Transport-Linked Ultrastructural Transformations in Mitochondria — J. Cell Biol.37, 342, 1968.

    Article  Google Scholar 

  15. Haldar D., Freeman K. B.: The Inhibition of Protein Synthesis and Respiration in Mouse Ascites Tumor Cells by Chloramphenicol and Its Isomeres and Analogues — Canad. J. Biochem.46, 1009, 1968.

    CAS  Google Scholar 

  16. Jeljaszewicz J., Szmigielski S., Korbecki M., Zak C.: Histochemical Demonstration of Enzymatic Activity Changes in KB Cells Affected by Staphylococcal α- and β-Haemolysins — J. infect. Dis.115, 421, 1965.

    PubMed  CAS  Google Scholar 

  17. Korbecki M., Jeljaszewicz J.: Action of Staphylococcal Toxins in Cell Cultures — J. infect. Dis.115, 205, 1965.

    PubMed  CAS  Google Scholar 

  18. Laiho K. U., Trump B. F.: Studies on the Pathogenesis of Cell Injury. Effects of Inhibitors of Metabolism and Membrane Function on the Mitochondria of Ehrlich Ascites Tumor Cells — Lab. Invest.82, 163, 1975.

    Google Scholar 

  19. Lasfargues E., Delaunay A.: Les cultures des tissus appliquées à la solution des problèmes immunologiques. I. Étude du pouvoir nécrosant des toxines microbiennesin vitro — Ann. Inst. Pasteur72, 38, 1946.

    Google Scholar 

  20. Lehninger A. L.: Water Uptake and Extrusion by Mitochondria in Relation to Oxidative Phosphorylation — Physiol. Rev.42, 467, 1962.

    PubMed  CAS  Google Scholar 

  21. Madoff M. A., Artenstein M. S., Weinstein I.: Studies on the Biologic Activity of Purified Staphylococcal α-Toxin. II. The Effect of α-Toxin on Ehrlich Ascites Carcinoma Cells — Yale J. Biol. Med.35, 382, 1963.

    Google Scholar 

  22. Maheswaran S. K., Frommes S. P., Lindorfer R. K.: Ultrastructural Changes in Neutrophils Treated with Staphylococcal α-Toxin — Canad. J. Microbiol.15, 128, 1969.

    CAS  Google Scholar 

  23. Manohar M., Maheswaran S. K., Frommes S. P., Lindorfer R. K.: Platelet Damaging Factor, a Fifth Activity of Staphylococcal α-Toxin — J. Bact.94, 224, 1967.

    PubMed  CAS  Google Scholar 

  24. Möllenhauer H. H.: Plastic Embedding Mixtures for Use in Electron Microscopy — Stain Technol.39, 111, 1964.

    PubMed  Google Scholar 

  25. Muscatello U., Guarriero-Bobyleva V., Pasquali-Ronchetti I., Ballotti-Ricci A. M.: Configurational Changes in Isolated Rat Liver Mitochondria as Revealed by Negative Staining. III. Modification Caused by Uncoupling Agents — J. Ultrastruct. Res. (In Press).

  26. Novák E., Seifert J., Buchar E., Rasková H.: Effect of Staphylococcal α-Toxin on the Phosphorylation of ADP by Rat Liver Mitochondria. I. Inhibition of Phosphorylation by a Thermo-Stable Factor — Toxicon9, 211, 1971.

    Article  PubMed  Google Scholar 

  27. Novák E., Seifert J., Rasková H.: Effect of Staphylococcal α-Toxin on Mitochondrial Mg++ (Na+ and K+) Activated Adenosine-Triphosphatase — Toxicon8, 261, 1970.

    Article  PubMed  Google Scholar 

  28. Packer L.: Metabolic and Structural States of Mitochondria. I. Regulation by Adenosine Diphosphate — J. biol. Chem.235, 242, 1960.

    PubMed  CAS  Google Scholar 

  29. Packer L.: Size and Shape Transformations Correlated with Oxidative Phosphorylation in Mitochondria. I. Swelling-Shrinkage Mechanism in Intact Mitochondria — J. Cell Biol.18, 487, 1963.

    Article  PubMed  CAS  Google Scholar 

  30. Paradisi F.: Mitochondrial Swelling Induced by Diphtheria Toxinin Vivo: A Comparison with the Action of Some Other Bacterial Toxins — Experientia (Basel)23, 1045, 1967.

    CAS  Google Scholar 

  31. Paradisi F., Graziano L.: The Action ofStaphylococcus α-Toxin on Cell Cultures: An Interference-Contrast Microscope Study — Experientia (Basel)28, 679, 1972.

    CAS  Google Scholar 

  32. Paradisi F., Graziano L.: Enzyme Cytochemistry of Cell Cultures Subjected to the Action ofStaphylococcus α-Toxin — Histochemie32, 81, 1972.

    PubMed  CAS  Google Scholar 

  33. Rahal J. J., Keusch G. T., Weinstein I.: Uncoupling of Oxidative Phosphorylation by Purified Staphylococcal α-Toxin — J. Lab. clin. Med.75, 442, 1970.

    PubMed  CAS  Google Scholar 

  34. Rahal J. J., Plaut E., Weinstein I.: Effect of Purified Staphylococcal α-Toxin on Active Sodium Transport and Aerobic Respiration in the Isolated Toad Bladder — J. clin. Invest.47, 1603, 1968.

    PubMed  CAS  Google Scholar 

  35. Reynolds E. S.: The Use of Lead Citrate at High pH as an Electron-Opaque Stain in Electron Microscopy — J. Cell Biol.17, 208, 1963.

    Article  PubMed  CAS  Google Scholar 

  36. Saladino A. J., Trump B. F.: Ion Movements in Cell Injury. Effects of Inhibition of Respiration and Glycolysis on the Ultrastructure and Function of the Epithelial Cells of the Toad Bladder — Amer. J. Path.52, 737, 1968.

    PubMed  CAS  Google Scholar 

  37. Thal A. P., Egner W. E.: The Site of Action of Staphylococcal α-Toxin — J. exp. Med.113, 67, 1961.

    Article  PubMed  CAS  Google Scholar 

  38. Thelestam M.: Effects ofStaphylococcus aureus Haemolysins on the Plasma Membrane of Cultured Mammalian Cells — In: Proceedings of the 3rd International Symposium onStaphylococci and Staphylococcal Infections. Warsaw, September 1975.

  39. Thelestam M., Möllby R.: Determination of Toxin Induced Leakage of Different Size Nucleotides through the Plasma Membrane of Human Diploid Fibroblasts — Infect. Immunity11, 640, 1975.

    CAS  Google Scholar 

  40. Thelestam M., Möllby R.: A Sensitive Assay for Detection of Toxin Induced Damage to the Cytoplasmic Membrane of Human Diploid Fibroblasts — Infect. Immunity12, 225, 1975.

    CAS  Google Scholar 

  41. Thelestam M., Möllby R., Wadström T.: Effects of Staphylococcal α-, β-, δ- and γ-Haemolysins on Human Diploid Fibroblasts and HeLa Cells: Evaluation of a New Quantitative Assay for Measuring Cell Damage — Infect. Immunity8, 938, 1973.

    CAS  Google Scholar 

  42. Wadström T.: Studies on Extracellular Proteins fromStaphylococcus aureus. IV. Purification of α-Toxin by Isoelectric Focusing — Biochim. biophys. Acta (Amst.)168, 228, 1968.

    Google Scholar 

  43. Wiseman G. M., Caird J. B.: Mode of Action of the α-Toxin ofStaphylococcus aureus — Canad. J. Microbiol.16, 47, 1970.

    CAS  Google Scholar 

  44. Wiseman G. M., Caird J. B.: Further Observations on the Mode of Action of the α-Toxin ofStaphylococcus aureus ‘Wood 46’ — Canad. J. Microbiol.18, 987, 1972.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Clinica Medica Generale e Terapia Medica, II Facoltà di Medicina e Chirurgia dell’Università di Napoli, Via S. Pansini 5, 80131, Napoli, Italia

    Franco Paradisi (Professor of Infectious Diseases), Gabriella Pepe & Alda Cifarelli

  2. Facoltà di Medicina e Chirurgia dell’Università di Roma, I Cattedra di Anatomia ed Istologia Patologica, Italia

    Paola Barsotti

  3. University of Chieti, Italy

    Franco Paradisi (Professor of Infectious Diseases)

Authors
  1. Franco Paradisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Barsotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriella Pepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alda Cifarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paradisi, F., Barsotti, P., Pepe, G. et al. Ultrastructural changes in HEp-2 cells treated with staphylococcal α-toxin. La Ricerca Clin. Lab. 6, 136–148 (1976). https://doi.org/10.1007/BF02949083

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02949083

Key-words

Search

Navigation