Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury

ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus 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...

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Autores principales:	Wilmara Salgado-Pabón, Laura Breshears, Adam R. Spaulding, Joseph A. Merriman, Christopher S. Stach, Alexander R. Horswill, Marnie L. Peterson, Patrick M. Schlievert
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/087a7cfde4974936adf96af1a510b9e6
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spelling	oai:doaj.org-article:087a7cfde4974936adf96af1a510b9e62021-11-15T15:43:08ZSuperantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury10.1128/mBio.00494-132150-7511https://doaj.org/article/087a7cfde4974936adf96af1a510b9e62013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00494-13https://doaj.org/toc/2150-7511ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus 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.Wilmara Salgado-PabónLaura BreshearsAdam R. SpauldingJoseph A. MerrimanChristopher S. StachAlexander R. HorswillMarnie L. PetersonPatrick M. SchlievertAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Wilmara Salgado-Pabón Laura Breshears Adam R. Spaulding Joseph A. Merriman Christopher S. Stach Alexander R. Horswill Marnie L. Peterson Patrick M. Schlievert Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
description	ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus 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.
format	article
author	Wilmara Salgado-Pabón Laura Breshears Adam R. Spaulding Joseph A. Merriman Christopher S. Stach Alexander R. Horswill Marnie L. Peterson Patrick M. Schlievert
author_facet	Wilmara Salgado-Pabón Laura Breshears Adam R. Spaulding Joseph A. Merriman Christopher S. Stach Alexander R. Horswill Marnie L. Peterson Patrick M. Schlievert
author_sort	Wilmara Salgado-Pabón
title	Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
title_short	Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
title_full	Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
title_fullStr	Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
title_full_unstemmed	Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury
title_sort	superantigens are critical for <named-content content-type="genus-species">staphylococcus aureus</named-content> infective endocarditis, sepsis, and acute kidney injury
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/087a7cfde4974936adf96af1a510b9e6
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Superantigens Are Critical for <named-content content-type="genus-species">Staphylococcus aureus</named-content> Infective Endocarditis, Sepsis, and Acute Kidney Injury

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