title: A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin.
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.
authors: Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Erik
authors: E
authors: Richter
authors: Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Manuela
authors: M
authors: Harms
authors: Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Katharina
authors: K
authors: Ventz
authors: Department of Biochemistry, University of Greifswald, 17487, Greifswald, Germany.
authors: Philipp
authors: P
authors: Gierok
authors: Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Ravi Kumar
authors: RK
authors: Chilukoti
authors: Animal Physiology and Biochemistry, Zoological Institute, University of Greifswald, 17487, Greifswald, Germany.
authors: Jan-Peter
authors: JP
authors: Hildebrandt
authors: Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Jörg
authors: J
authors: Mostertz
authors: Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17489, Greifswald, Germany.
authors: Falko
authors: F
authors: Hochgräfe
mesh_terms: D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity*; D002460:Cell Line; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System; D009928:Organ Specificity; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D020543:Proteome; C021091:staphylococcal alpha-toxin; D066246:ErbB Receptors