Abstract 11644: Infective Endocarditis Due to Staphylococcus Aureus and Lethality Are Critically Dependent on the Action of Superantigens
Introduction: Staphylococcus aureus infective endocarditis (IE) is an aggressive infection of the heart, predominantly the valves, that is fulminant and becomes life threatening in a matter of days. It affects ~40,000 individuals each year in the US, resulting in ~12,000 strokes and 20,000 deaths. In S. aureus illnesses, superantigens (SAgs) cause lethality through massive immune system activation and their effects on the cardiovasculature, eliciting capillary leak and hypotension. Up to 90% of S. aureus IE isolates encode for the enterotoxin gene cluster (egc) SAgs, 9-20% for toxic shock syndrome toxin-1 (TSST-1), and 18-25% for staphylococcal enterotoxin C (SEC). SEC is critical for vegetation formation and death in S. aureus MW2, a human isolate exceptional at causing IE in rabbits. Here, we addressed the contribution of egc SAgs and TSST-1 to expand on the role of SAgs to IE disease severity and outcomes.
Methods: In this study, we tested S. aureus strain MN8, a human isolate that causes IE in rabbits and produces TSST-1 and egc SAgs, and SAg deletion isogenic variants in the rabbit model of native valve, left-sided IE.
Results: Deletion of tstH and the egc significantly reduced vegetation size and increased survival. However, TSST-1 and the egc SAgs have differential effects on survival. tstH deletion leads to rabbit survival similar to that of infection with tstHegc, while the egc deletion leads to lethality resembling that of wildtype. While tstH deletion increases survival, it still results in large septic vegetations and late lethality in 50% of rabbits. Furthermore, expression of TSST-1 or egc SAgs in SAg negative strains results in large septic vegetations, demonstrating that production of SAgs is sufficient to allow an otherwise avirulent strain to cause IE.
Conclusion: The egc SAgs, TSST-1 and SEC are critical contributors to the etiology and fatal outcomes characteristic of S. aureus IE. A decrease in morbidity and mortality due to S. aureus IE may be feasible with standard of care that incorporates SAg neutralizing agents or SAg production inhibitors to allow antimicrobial therapy to take on its full effect.
Author Disclosures: C.S. Stach: None. B.G. Vu: None. J.A. Merriman: None. A. Herrera: None. P.M. Schlievert: None. W. Salgado-Pabón: None.
- © 2014 by American Heart Association, Inc.