A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin
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 underst...
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| Veröffentlicht in: | PloS one 2015-03, Vol.10 (3), p.e0122089-e0122089 |
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| creator | Richter, Erik Harms, Manuela Ventz, Katharina Gierok, Philipp Chilukoti, Ravi Kumar Hildebrandt, Jan-Peter Mostertz, Jörg Hochgräfe, Falko |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0122089 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0122089</identifier><identifier>PMID: 25816343</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Activation ; Amino acids ; Antigenic determinants ; Bacterial Toxins - immunology ; Bacterial Toxins - toxicity ; Biochemistry ; Biology ; Cancer ; Cell culture ; Cell death ; Cell growth ; Cell Line ; Cell lines ; Cell survival ; Cystic fibrosis ; Cytoskeleton ; Cytotoxicity ; Epidermal growth factor ; Epidermal growth factor receptors ; Epithelial cells ; Gene expression ; Genomics ; Hemolysin Proteins - immunology ; Hemolysin Proteins - toxicity ; Humans ; Kinases ; MAP Kinase Signaling System ; Medical research ; Organ Specificity ; Phosphatase ; Phosphorylation ; Phosphotransferases ; Proteins ; Proteome - genetics ; Proteome - metabolism ; Receptor, Epidermal Growth Factor - genetics ; Receptor, Epidermal Growth Factor - metabolism ; Respiratory Mucosa - drug effects ; Respiratory Mucosa - immunology ; Respiratory Mucosa - metabolism ; Respiratory tract ; Signaling ; Staphylococcus aureus ; Transcription ; α-Toxin</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0122089-e0122089</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Richter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Richter et al 2015 Richter et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ecbf7804073b8007c5b4f648e82b540dffe223a2a0d7f6a791c77f0868deb4503</citedby><cites>FETCH-LOGICAL-c692t-ecbf7804073b8007c5b4f648e82b540dffe223a2a0d7f6a791c77f0868deb4503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376684/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376684/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25816343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Richter, Erik</creatorcontrib><creatorcontrib>Harms, Manuela</creatorcontrib><creatorcontrib>Ventz, Katharina</creatorcontrib><creatorcontrib>Gierok, Philipp</creatorcontrib><creatorcontrib>Chilukoti, Ravi Kumar</creatorcontrib><creatorcontrib>Hildebrandt, Jan-Peter</creatorcontrib><creatorcontrib>Mostertz, Jörg</creatorcontrib><creatorcontrib>Hochgräfe, Falko</creatorcontrib><title>A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Responsiveness of cells to alpha-toxin (Hla) from Staphylococcus aureus appears to occur in a cell-type dependent manner. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25816343</pmid><doi>10.1371/journal.pone.0122089</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0122089-e0122089 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1667159300 |
| source | Public Library of Science (PLoS) Journals Open Access; PubMed (Medline); MEDLINE; Full-Text Journals in Chemistry (Open access); Directory of Open Access Journals; EZB Electronic Journals Library |
| subjects | Actin Activation Amino acids Antigenic determinants Bacterial Toxins - immunology Bacterial Toxins - toxicity Biochemistry Biology Cancer Cell culture Cell death Cell growth Cell Line Cell lines Cell survival Cystic fibrosis Cytoskeleton Cytotoxicity Epidermal growth factor Epidermal growth factor receptors Epithelial cells Gene expression Genomics Hemolysin Proteins - immunology Hemolysin Proteins - toxicity Humans Kinases MAP Kinase Signaling System Medical research Organ Specificity Phosphatase Phosphorylation Phosphotransferases Proteins Proteome - genetics Proteome - metabolism Receptor, Epidermal Growth Factor - genetics Receptor, Epidermal Growth Factor - metabolism Respiratory Mucosa - drug effects Respiratory Mucosa - immunology Respiratory Mucosa - metabolism Respiratory tract Signaling Staphylococcus aureus Transcription α-Toxin |
| title | A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T17%3A20%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20multi-omics%20approach%20identifies%20key%20hubs%20associated%20with%20cell%20type-specific%20responses%20of%20airway%20epithelial%20cells%20to%20staphylococcal%20alpha-toxin&rft.jtitle=PloS%20one&rft.au=Richter,%20Erik&rft.date=2015-03-27&rft.volume=10&rft.issue=3&rft.spage=e0122089&rft.epage=e0122089&rft.pages=e0122089-e0122089&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0122089&rft_dat=%3Cgale_plos_%3EA421800633%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1667159300&rft_id=info:pmid/25816343&rft_galeid=A421800633&rft_doaj_id=oai_doaj_org_article_d1d45e8c5d6b42ce9627f50e12dd983b&rfr_iscdi=true |