1887

Abstract

The 1928 Bundaberg disaster is one of the greatest vaccine tragedies in history. Of 21 children immunized with a diphtheria toxin–antitoxin preparation contaminated with , 18 developed life-threatening disease and 12 died within 48 h. Historically, the deaths have been attributed to α-toxin, a secreted cytotoxin produced by most strains, yet the ability of the Bundaberg contaminant microbe to produce the toxin has never been verified. For the first time, the ability of the original strain to produce α-toxin and other virulence factors is investigated. The study investigates the genetic and regulatory loci mediating α-toxin expression by PCR and assesses production of the cytotoxin using an erythrocyte haemolysis assay. This analysis is extended to other secreted virulence factors produced by the strain, and their sufficiency to cause lethality in New Zealand white rabbits is determined. Although the strain possesses a wild-type allele for α-toxin, it must have a defective regulatory system, which is responsible for the strain's minimal α-toxin production. The strain encodes and produces staphylococcal superantigens, including toxic shock syndrome toxin-1 (TSST-1), which is sufficient to cause lethality in patients. The findings cast doubt on the belief that α-toxin is the major virulence factor responsible for the Bundaberg fatalities and point to the superantigen TSST-1 as the cause of the disaster.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000196
2015-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/161/12/2361.html?itemId=/content/journal/micro/10.1099/mic.0.000196&mimeType=html&fmt=ahah

References

  1. Royal Commission of Inquiry into the Fatalities at Bundaberg (1928). Report of the Royal Commission of Inquiry into the Fatalities at BundabergCanberraH. J. Green. [Google Scholar]
  2. Berube B. J., Bubeck Wardenburg J. (2013). Staphylococcus aureus α-toxin: nearly a century of intrigueToxins (Basel) 511401166 [View Article][PubMed]. [Google Scholar]
  3. Bhakdi S., Tranum-Jensen J. (1991). Alpha-toxin of Staphylococcus aureusMicrobiol Rev 55733751[PubMed]. [Google Scholar]
  4. Blake M. S., Johnston K. H., Russell-Jones G. J., Gotschlich E. C. (1984). A rapid, sensitive method for detection of alkaline phosphatase-conjugated anti-antibody on Western blotsAnal Biochem 136175179 [View Article][PubMed]. [Google Scholar]
  5. Blomster-Hautamaa D. A., Schlievert P. M. (1988). Preparation of toxic shock syndrome toxin-1.Methods Enzymol 1653743 [View Article][PubMed]. [Google Scholar]
  6. Blomster-Hautamaa D. A., Kreiswirth B. N., Novick R. P., Schlievert P. M. (1986). Resolution of highly purified toxic-shock syndrome toxin 1 into two distinct proteins by isoelectric focusingBiochemistry 255459 [View Article][PubMed]. [Google Scholar]
  7. Burnet F. M. (1929). The exotoins of Staphylococcus pyogenes aureusJ Pathol Bacteriol 32717733 [View Article]. [Google Scholar]
  8. Cheung G. Y., Duong A. C., Otto M. (2012). Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and pathogenesisMicrobes Infect 14380386 [View Article][PubMed]. [Google Scholar]
  9. Davis J. P., Chesney P. J., Wand P. J., LaVenture M. (1980). Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and preventionN Engl J Med 30314291435 [View Article][PubMed]. [Google Scholar]
  10. Dinges M. M., Orwin P. M., Schlievert P. M. (2000). Exotoxins of Staphylococcus aureusClin Microbiol Rev 131634 [View Article][PubMed]. [Google Scholar]
  11. Flack C. E., Zurek O. W., Meishery D. D., Pallister K. B., Malone C. L., Horswill A. R., Voyich J. M. (2014). Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuliProc Natl Acad Sci U S A 111E2037E2045 [View Article][PubMed]. [Google Scholar]
  12. Geisinger E., Chen J., Novick R. P. (2012). Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureusJ Bacteriol 19428542864 [View Article][PubMed]. [Google Scholar]
  13. Glenny A. T., Stevens M. (1935). Staphylococcus toxins and antitoxinsJ Pathol Bacteriol 40201210 [View Article]. [Google Scholar]
  14. Jarraud S., Peyrat M. A., Lim A., Tristan A., Bes M., Mougel C., Etienne J., Vandenesch F., Bonneville M., Lina G. (2001). egc, A highly prevalent operon of enterotoxin gene, forms a putative nursery of superantigens in Staphylococcus aureusJ Immunol 166669677 [View Article][PubMed]. [Google Scholar]
  15. John C. C., Niermann M., Sharon B., Peterson M. L., Kranz D. M., Schlievert P. M. (2009). Staphylococcal toxic shock syndrome erythroderma is associated with superantigenicity and hypersensitivityClin Infect Dis 4918931896 [View Article][PubMed]. [Google Scholar]
  16. Lina G., Bohach G. A., Nair S. P., Hiramatsu K., Jouvin-Marche E.,, Mariuzza R. & International Nomenclature Committee for Staphylococcal Superantigens (2004). Standard nomenclature for the superantigens expressed by StaphylococcusJ Infect Dis 18923342336 [View Article][PubMed]. [Google Scholar]
  17. Mairpady Shambat S., Haggar A., Vandenesch F., Lina G., van Wamel W. J., Arakere G., Svensson M., Norrby-Teglund A. (2014). Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolatesPLoS One 9e106107 [View Article][PubMed]. [Google Scholar]
  18. Nowrouzian F. L., Ali A., Badiou C., Dauwalder O., Lina G., Josefsson E. (2015). Impacts of enterotoxin gene cluster-encoded superantigens on local and systemic experimental Staphylococcus aureus infectionsEur J Clin Microbiol Infect Dis 3414431449 [View Article][PubMed]. [Google Scholar]
  19. Pang Y. Y., Schwartz J., Thoendel M., Ackermann L. W., Horswill A. R., Nauseef W. M. (2010). agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophilsJ Innate Immun 2546559 [View Article][PubMed]. [Google Scholar]
  20. Pragman A. A., Schlievert P. M. (2004). Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulationFEMS Immunol Med Microbiol 42147154 [View Article][PubMed]. [Google Scholar]
  21. Priest B. P., Schlievert P. M., Dunn D. L. (1989). Treatment of toxic shock syndrome with endotoxin-neutralizing antibodyJ Surg Res 46527531 [View Article][PubMed]. [Google Scholar]
  22. Salgado-Pabón W., Case-Cook L. C., Schlievert P. M. (2014). Molecular analysis of staphylococcal superantigensMethods Mol Biol 1085169185 [View Article][PubMed]. [Google Scholar]
  23. Schlievert P. M. (1982). Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type CInfect Immun 36123128[PubMed]. [Google Scholar]
  24. Schlievert P. M. (1988). Immunochemical assays for toxic shock syndrome toxin-1Methods Enzymol 165339344 [View Article][PubMed]. [Google Scholar]
  25. Shands K. N., Schmid G. P., Dan B. B., Blum D., Guidotti R. J., Hargrett N. T., Anderson R. L., Hill D. L., Broome C. V., other authors. (1980). Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 casesN Engl J Med 30314361442 [View Article][PubMed]. [Google Scholar]
  26. Spaulding A. R., Lin Y. C., Merriman J. A., Brosnahan A. J., Peterson M. L., Schlievert P. M. (2012). Immunity to Staphylococcus aureus secreted proteins protects rabbits from serious illnessesVaccine 3050995109 [View Article][PubMed]. [Google Scholar]
  27. Spaulding A. R., Salgado-Pabón W., Kohler P. L., Horswill A. R., Leung D. Y., Schlievert P. M. (2013). Staphylococcal and streptococcal superantigen exotoxinsClin Microbiol Rev 26422447 [View Article][PubMed]. [Google Scholar]
  28. Stich N., Waclavicek M., Model N., Eibl M. M. (2010). Staphylococcal superantigen (TSST-1) mutant analysis reveals that T cell activation is required for biological effects in the rabbit including the cytokine stormToxins 222722288 [View Article][PubMed]. [Google Scholar]
  29. Thoendel M., Kavanaugh J. S., Flack C. E., Horswill A. R. (2011). Peptide signaling in the staphylococciChem Rev 111117151 [View Article][PubMed]. [Google Scholar]
  30. Todd J., Fishaut M., Kapral F., Welch T. (1978). Toxic-shock syndrome associated with phage-group-I staphylococciLancet 31211161118 [View Article][PubMed]. [Google Scholar]
  31. Vu B. G., Stach C. S., Salgado-Pabón W., Diekema D. J., Gardner S. E., Schlievert P. M. (2014). Superantigens of Staphylococcus aureus from patients with diabetic foot ulcersJ Infect Dis 21019201927 [View Article][PubMed]. [Google Scholar]
  32. Westphal O., Luderitz O., Keiderling W. (1952). [Effects of bacterial toxins; biochemical analysis of inflammation]Zentralbl Bakteriol Parasitenkd Infektionskr Hyg 158152160[PubMed]. [Google Scholar]
  33. Wiseman G. M. (1975). The hemolysins of Staphylococcus aureusBacteriol Rev 39317344[PubMed]. [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000196
Loading
/content/journal/micro/10.1099/mic.0.000196
Loading

Data & Media loading...

Supplements

Supplementary Data



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error