title: Toxic shock syndrome toxin-1, not α-toxin, mediated Bundaberg fatalities.
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 Staphylococcus aureus, 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 S. aureus 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 in vitro 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.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mueller
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Merriman
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
mesh_terms: D000818:Animals; D001315:Australia; D001427:Bacterial Toxins / Q000633:toxicity*; D004768:Enterotoxins / Q000633:toxicity*; D006801:Humans; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D018089:Superantigens / Q000633:toxicity*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal