Co-production of staphylococcal enterotoxin A with toxic shock syndrome toxin-1 (TSST-1) enhances TSST-1 mediated mortality in a D-galactosamine sensitized mouse model of lethal shock

It has previously been reported that staphylococcal enterotoxin A (SEA) is frequently co-expressed with toxic shock syndrome toxin-1 (TSST-1) in menst rual Toxic Shock Syndrome (MTSS)-associated Staphylococcus aureus. It was h ypothesized that cc-production of SEA and TSST-1 might yield a more virulen t strain than one that produced TSST-1 but not SEA. To test this hypothesis , a TSST-1 1(+)/SEA(-) derivative of S. aureus RN3984 (TSST-1(+)/SEA(+)) wa s constructed by plasmid integration, and the isogenic pair were introduced into a D-galactosamine sensitized mouse model of lethal shock. At 72 h, 27 out of 30 (90%) mice inoculated with the parental strain died, as compared to 21 out of 30 (70%) mice inoculated with the isogenic derivative (P = 0. 05, Fisher's exact test; 1-tailed; 95% confidence limits, 0.80-20.80). Our results suggest that co-production of SEA with TSST-1 does enhance the abil ity of this strain of S. aureus to induce lethal shock in vivo. This enhanc ed virulence could be due to an additive or synergistic activity of the tox in combination on T cell proliferation and cytokine production in the anima l model. (C) 1999 Academic Press.