Journal article
Local Epidermal Growth Factor Receptor Signaling Mediates the Systemic Pathogenic Effects of Staphylococcus aureus Toxic Shock Syndrome
PloS one, Vol.11(7), e0158969
2016
DOI: 10.1371/journal.pone.0158969
PMCID: PMC4944920
PMID: 27414801
Abstract
Secreted factors of Staphylococcus aureus can activate host signaling from the epidermal growth factor receptor (EGFR). The superantigen toxic shock syndrome toxin-1 (TSST-1) contributes to mucosal cytokine production through a disintegrin and metalloproteinase (ADAM)-mediated shedding of EGFR ligands and subsequent EGFR activation. The secreted hemolysin, α-toxin, can also induce EGFR signaling and directly interacts with ADAM10, a sheddase of EGFR ligands. The current work explores the role of EGFR signaling in menstrual toxic shock syndrome (mTSS), a disease mediated by TSST-1. The data presented show that TSST-1 and α-toxin induce ADAM- and EGFR-dependent cytokine production from human vaginal epithelial cells. TSST-1 and α-toxin also induce cytokine production from an ex vivo porcine vaginal mucosa (PVM) model. EGFR signaling is responsible for the majority of IL-8 production from PVM in response to secreted toxins and live S. aureus. Finally, data are presented demonstrating that inhibition of EGFR signaling with the EGFR-specific tyrosine kinase inhibitor AG1478 significantly increases survival in a rabbit model of mTSS. These data indicate that EGFR signaling is critical for progression of an S. aureus exotoxin-mediated disease and may represent an attractive host target for therapeutics.
Details
- Title: Subtitle
- Local Epidermal Growth Factor Receptor Signaling Mediates the Systemic Pathogenic Effects of Staphylococcus aureus Toxic Shock Syndrome
- Creators
- Laura M Breshears - University of Minnesota, College of Pharmacy, Department of Experimental and Clinical Pharmacology, Minneapolis, Minnesota, United States of AmericaAaron N Gillman - University of Minnesota, College of Pharmacy, Department of Experimental and Clinical Pharmacology, Minneapolis, Minnesota, United States of AmericaChristopher S Stach - University of Minnesota, College of Biological Sciences, Biotechnology Institute, Minneapolis, Minnesota, United States of AmericaPatrick M Schlievert - University of Iowa, Carver College of Medicine, Department of Microbiology, Iowa City, Iowa, United States of AmericaMarnie L Peterson - University of Minnesota, College of Pharmacy, Department of Experimental and Clinical Pharmacology, Minneapolis, Minnesota, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(7), e0158969
- DOI
- 10.1371/journal.pone.0158969
- PMID
- 27414801
- PMCID
- PMC4944920
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: R01AI073366-03; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: R01AI074283
- Language
- English
- Date published
- 2016
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001146202771
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