Next Article in Journal
Occurrence of Regulated Mycotoxins and Other Microbial Metabolites in Dried Cassava Products from Nigeria
Next Article in Special Issue
Prevalence and Genetic Characteristics of Staphylococcus aureus and Staphylococcus argenteus Isolates Harboring Panton-Valentine Leukocidin, Enterotoxins, and TSST-1 Genes from Food Handlers in Myanmar
Previous Article in Journal
Survey of Alternaria Toxins and Other Mycotoxins in Dried Fruits in China
Previous Article in Special Issue
Virulence Genes of S. aureus from Dairy Cow Mastitis and Contagiousness Risk
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Toxins 2017, 9(7), 202; doi:10.3390/toxins9070202

Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa

1
Department of Pharmacy, University of Tromsø, Tromsø 9019, Troms, Norway
2
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
3
Extherid Biosciences, LLC., Jackson, WY 83001, USA
4
School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA
5
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
6
Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Shin-ichi Miyoshi
Received: 19 May 2016 / Revised: 2 June 2017 / Accepted: 9 June 2017 / Published: 28 June 2017
(This article belongs to the Collection Staphylococcus aureus Toxins)
View Full-Text   |   Download PDF [2828 KB, uploaded 28 June 2017]   |  

Abstract

Staphylococcus aureus (S. aureus) produces many different exotoxins including the gamma-toxins, HlgAB and HlgCB. Gamma-toxins form pores in both leukocyte and erythrocyte membranes, resulting in cell lysis. The genes encoding gamma-toxins are present in most strains of S. aureus, and are commonly expressed in clinical isolates recovered from menstrual Toxic Shock Syndrome (mTSS) patients. This study set out to investigate the cytotoxic and proinflammatory effects of gamma-toxins on vaginal epithelial surfaces. We found that both HlgAB and HlgCB were cytotoxic to cultured human vaginal epithelial cells (HVECs) and induced cytokine production at sub-cytotoxic doses. Cytokine production induced by gamma-toxin treatment of HVECs was found to involve epidermal growth factor receptor (EGFR) signaling and mediated by shedding of EGFR ligands from the cell surface. The gamma-toxin subunits displayed differential binding to HVECs (HlgA 93%, HlgB 97% and HlgC 28%) with both components (HlgAB or HlgCB) required for maximum detectable binding and significant stimulation of cytokine production. In studies using full thickness ex vivo porcine vaginal mucosa, HlgAB or HlgCB stimulated a dose-dependent cytokine response, which was reduced significantly by inhibition of EGFR signaling. The effects of gamma-toxins on porcine vaginal tissue and cultured HVECs were validated using ex vivo human ectocervical tissue. Collectively, these studies have identified the EGFR-signaling pathway as a key component in gamma-toxin-induced proinflammatory changes at epithelial surfaces and highlight a potential therapeutic target to diminish toxigenic effects of S. aureus infections. View Full-Text
Keywords: Staphylococcus aureus; gamma-toxin; epidermal growth factor receptor; menstrual toxic shock syndrome; tyrosine kinase inhibitors; and mucosal immune response Staphylococcus aureus; gamma-toxin; epidermal growth factor receptor; menstrual toxic shock syndrome; tyrosine kinase inhibitors; and mucosal immune response
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Gillman, A.N.; Breshears, L.M.; Kistler, C.K.; Finnegan, P.M.; Torres, V.J.; Schlievert, P.M.; Peterson, M.L. Epidermal Growth Factor Receptor Signaling Enhances the Proinflammatory Effects of Staphylococcus aureus Gamma-Toxin on the Mucosa. Toxins 2017, 9, 202.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top