Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuatedvirulence 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 to xin-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 Z ealand White (NZW) rabbits, using isogenic tst(+)/sea(+) S. aureus mutants in which rst 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 w ith the tst(+)/sea(+) strain compared to its tst(-)/sea(+) isogenic derivat ive (4/13 vs. 0/14; p < 0.05, Fisher's exact test, 2-tailed). Mean fever in dex 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 compar ed to the tst(-)/sea(+) isogenic derivative. Thus, regardless of the role o f 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 pathogen esis of MTSS with a MTSS-associated clinical S. aureus strain in a relevant animal model.