Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome.
Since menstrual toxic shock syndrome (MTSS) is associated with a predominant clone of Staphylococcus aureus which produces both toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), we sought to clarify the role of TSST-1 in a tampon-associated vaginal infection model in New Zealand White (NZW) rabbits, using isogenic tst+/sea+ S. aureus mutants in which tst was inactivated by allelic replacement. Rabbits infected with the tst-/sea+ strain became ill within 3 days, with fever, weight loss, conjunctival hyperemia, and lethargy. Mortality was significantly higher with the tst+/sea+ strain compared to its tst-/sea+ isogenic derivative (4/13 vs. 0/14; p < 0.05, Fisher's exact test, 2-tailed). Mean fever index was higher (p < 0.005; t test, 2-tailed) and weight loss more sustained among survivors in the tst+/sea+ group. Furthermore, culture filtrates from the tst+/sea+ strain induced a significantly greater response in mitogenesis and TNF alpha secretion from rabbit splenocytes in vitro compared to the tst-/sea+ isogenic derivative. Thus, regardless of the role of SEA, TSST-1 significantly contributed to both morbidity and mortality in this tampon-associated vaginal infection model in NZW rabbits. This is the first demonstration of the potential role of TSST-1 and SEA in the pathogenesis of MTSS with a MTSS-associated clinical S. aureus strain in a relevant animal model.
Department of Medicine, University of British Columbia, Vancouver, Canada.
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De Boer
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D000818:Animals; D001427:Bacterial Toxins; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D011817:Rabbits; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014774:Virulence
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal