Superantigens Are Critical for Staphylococcus aureusInfective Endocarditis, Sepsis, and Acute Kidney Injury

+Author Affiliations

Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAa
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USAb

Address correspondence to Patrick M. Schlievert, patrick-schlievert@uiowa.edu.

Editor Eric Johnson, University of Wisconsin

ABSTRACT

Infective endocarditis and kidney infections are serious complications ofStaphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses.

IMPORTANCE The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763–1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that superantigens are critical in the causation of all three infections. We show that their association results from both superantigenicity and direct toxic effects on endothelial cells, the latter likely contributing to delayed endothelium healing. Our studies contribute significantly to understanding the development of these illnesses and are expected to lead to development of important therapies to treat such illnesses.

This Article

doi: 10.1128/mBio.00494-1320 August 2013 mBio vol. 4 no. 4 e00494-13

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FOOTNOTES

Citation Salgado-Pabón W, Breshears L, Spaulding AR, Merriman JA, Stach CS, Horswill AR, Peterson ML, Schlievert PM. 2013. Superantigens are critical forStaphylococcus aureus infective endocarditis, sepsis, and acute kidney injury. mBio 4(4):e00494-13. doi:10.1128/mBio.00494-13.

Received 8 July 2013
Accepted 29 July 2013
Published 20 August 2013

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