A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin

PLoS One. 2015 Mar 27;10(3):e0122089. doi: 10.1371/journal.pone.0122089. eCollection 2015.

Abstract

Responsiveness of cells to alpha-toxin (Hla) from Staphylococcus aureus appears to occur in a cell-type dependent manner. Here, we compare two human bronchial epithelial cell lines, i.e. Hla-susceptible 16HBE14o- and Hla-resistant S9 cells, by a quantitative multi-omics strategy for a better understanding of Hla-induced cellular programs. Phosphoproteomics revealed a substantial impact on phosphorylation-dependent signaling in both cell models and highlights alterations in signaling pathways associated with cell-cell and cell-matrix contacts as well as the actin cytoskeleton as key features of early rHla-induced effects. Along comparable changes in down-stream activity of major protein kinases significant differences between both models were found upon rHla-treatment including activation of the epidermal growth factor receptor EGFR and mitogen-activated protein kinases MAPK1/3 signaling in S9 and repression in 16HBE14o- cells. System-wide transcript and protein expression profiling indicate induction of an immediate early response in either model. In addition, EGFR and MAPK1/3-mediated changes in gene expression suggest cellular recovery and survival in S9 cells but cell death in 16HBE14o- cells. Strikingly, inhibition of the EGFR sensitized S9 cells to Hla indicating that the cellular capacity of activation of the EGFR is a major protective determinant against Hla-mediated cytotoxic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / immunology
  • Bacterial Toxins / toxicity*
  • Cell Line
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Hemolysin Proteins / immunology
  • Hemolysin Proteins / toxicity*
  • Humans
  • MAP Kinase Signaling System*
  • Organ Specificity
  • Proteome / genetics
  • Proteome / metabolism*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*

Substances

  • Bacterial Toxins
  • Hemolysin Proteins
  • Proteome
  • staphylococcal alpha-toxin
  • ErbB Receptors

Associated data

  • GEO/GSE65018

Grant support

This study was supported by funds from the Bundesministerium für Bildung und Forschung (http://www.unternehmen-region.de/) to FH (03Z1CN21). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.