Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis

Christopher S Stach; Bao G Vu; Joseph A Merriman; Alfa Herrera; Michael P Cahill; Patrick M Schlievert; Wilmara Salgado-Pabón

doi:10.1371/journal.pone.0154762

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Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis

Journal article

Open access

Peer reviewed

Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis

Christopher S Stach, Bao G Vu, Joseph A Merriman, Alfa Herrera, Michael P Cahill, Patrick M Schlievert and Wilmara Salgado-Pabón

PloS one, Vol.11(4), pp.e0154762-e0154762

2016

DOI: 10.1371/journal.pone.0154762

PMCID: PMC4849672

PMID: 27124393

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Abstract

Superantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens. We examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis. TSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis. Our studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis.

Staphylococcus aureus - genetics

Rabbits

Male

Superantigens - immunology

Staphylococcus aureus - pathogenicity

Shock, Septic - microbiology

Anti-Bacterial Agents - therapeutic use

Enterotoxins - genetics

Animals

Immunoglobulins, Intravenous - therapeutic use

Vancomycin - therapeutic use

Superantigens - genetics

Endocarditis, Bacterial - microbiology

Bacterial Toxins - genetics

Female

Staphylococcus aureus - immunology

Staphylococcal Infections - microbiology

Drug Therapy, Combination

Sepsis - microbiology

Disease Models, Animal

Immunologic Factors - therapeutic use

Details

Title: Subtitle: Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis
Creators: Christopher S Stach - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Bao G Vu - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Joseph A Merriman - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Alfa Herrera - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Michael P Cahill - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Patrick M Schlievert - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Wilmara Salgado-Pabón - Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.11(4), pp.e0154762-e0154762
DOI: 10.1371/journal.pone.0154762
PMID: 27124393
PMCID: PMC4849672
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Language: English
Date published: 2016
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001142802771

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