A Multi-Omics Approach Identifies Key Hubs Associated with Cell Type-Specific Responses of Airway Epithelial Cells to Staphylococcal Alpha-Toxin

作者：Richter Erik; Harms Manuela; Ventz Katharina; Gierok Philipp; Chilukoti Ravi Kumar; Hildebrandt Jan Peter; Mostertz Joerg; Hochgraefe Falko

来源：PLos One, 2015, 10(3): UNSP e0122089.

DOI：10.1371/journal.pone.0122089

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.

• 出版日期2015-3-27