Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung
Abstract
Background: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(-/-) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(-/-) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. Results: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(-/-) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infectionmore »
- Authors:
-
[1];
- Univ. of Illinois, Chicago, IL (United States)
- Univ. of Chicago, IL (United States)
- Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH); USDOE
- OSTI Identifier:
- 1607643
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- BMC Genomics
- Additional Journal Information:
- Journal Volume: 20; Journal Issue: 1; Journal ID: ISSN 1471-2164
- Publisher:
- Springer
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Lung infection; Gene Profiling; Pseudomonas aeruginosa; Resistance to Infection; Sphingolipids; Sphingosine kinase 2
Citation Formats
Ebenezer, David L., Fu, Panfeng, Krishnan, Yashaswin, Maienschein-Cline, Mark, Hu, Hong, Jung, Segun, Madduri, Ravi, Arbieva, Zarema, Harijith, Anantha, and Natarajan, Viswanathan. Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung. United States: N. p., 2019.
Web. doi:10.1186/s12864-019-6367-9.
Ebenezer, David L., Fu, Panfeng, Krishnan, Yashaswin, Maienschein-Cline, Mark, Hu, Hong, Jung, Segun, Madduri, Ravi, Arbieva, Zarema, Harijith, Anantha, & Natarajan, Viswanathan. Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung. United States. https://doi.org/10.1186/s12864-019-6367-9
Ebenezer, David L., Fu, Panfeng, Krishnan, Yashaswin, Maienschein-Cline, Mark, Hu, Hong, Jung, Segun, Madduri, Ravi, Arbieva, Zarema, Harijith, Anantha, and Natarajan, Viswanathan. Mon .
"Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung". United States. https://doi.org/10.1186/s12864-019-6367-9. https://www.osti.gov/servlets/purl/1607643.
@article{osti_1607643,
title = {Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung},
author = {Ebenezer, David L. and Fu, Panfeng and Krishnan, Yashaswin and Maienschein-Cline, Mark and Hu, Hong and Jung, Segun and Madduri, Ravi and Arbieva, Zarema and Harijith, Anantha and Natarajan, Viswanathan},
abstractNote = {Background: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(-/-) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(-/-) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. Results: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(-/-) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-kappa B signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. Conclusion: Using Sphk2(-/-) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.},
doi = {10.1186/s12864-019-6367-9},
journal = {BMC Genomics},
number = 1,
volume = 20,
place = {United States},
year = {2019},
month = {12}
}
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Works referenced in this record:
Mucoid conversion of Pseudomonas aeruginos by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung
journal, June 1999
- Mathee, Kalai; Ciofu, Oana; Sternberg, Claus
- Microbiology, Vol. 145, Issue 6
Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients
journal, April 2004
- Al-Aloul, M.
- Thorax, Vol. 59, Issue 4
Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis Lungs
journal, January 2017
- Kovacic, Barbara; Sehl, Carolin; Wilker, Barbara
- Cellular Physiology and Biochemistry, Vol. 41, Issue 3
The Stringent Response Controls Catalases in Pseudomonas aeruginosa and Is Required for Hydrogen Peroxide and Antibiotic Tolerance
journal, March 2013
- Khakimova, M.; Ahlgren, H. G.; Harrison, J. J.
- Journal of Bacteriology, Vol. 195, Issue 9
Differential regulation of sphingosine kinases 1 and 2 in lung injury
journal, April 2009
- Wadgaonkar, Raj; Patel, Vipul; Grinkina, Natalia
- American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 296, Issue 4
Protective Effects of Sphingosine 1-Phosphate in Murine Endotoxin-induced Inflammatory Lung Injury
journal, June 2004
- Peng, Xinqi; Hassoun, Paul M.; Sammani, Saad
- American Journal of Respiratory and Critical Care Medicine, Vol. 169, Issue 11
RASGRP2 Suppresses Apoptosis via Inhibition of ROS Production in Vascular Endothelial Cells
journal, January 2019
- Sato, Takuma; Takino, Jun-ichi; Nagamine, Kentaro
- The Scientific World Journal, Vol. 2019
Polyphenol compounds and PKC signaling
journal, October 2016
- Das, Joydip; Ramani, Rashmi; Suraju, M. Olufemi
- Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1860, Issue 10
Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease
journal, February 1997
- Li, J. -D.; Dohrman, A. F.; Gallup, M.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 3
Ceramide in bacterial infections and cystic fibrosis
journal, November 2008
- Grassmé, Heike; Becker, Katrin Anne; Zhang, Yang
- Biological Chemistry, Vol. 389, Issue 11
Nonlinear partial differential equations and applications: A simple alfalfa seedling infection model for Pseudomonas aeruginosa strains associated with cystic fibrosis shows AlgT (sigma-22) and RhlR contribute to pathogenesis
journal, November 2002
- Silo-Suh, L.; Suh, S. -J.; Sokol, P. A.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 24
Quantitative Reduction of the TCR Adapter Protein SLP-76 Unbalances Immunity and Immune Regulation
journal, February 2015
- Siggs, Owen M.; Miosge, Lisa A.; Daley, Stephen R.
- The Journal of Immunology, Vol. 194, Issue 6
Pseudomonas Exotoxin A: optimized by evolution for effective killing
journal, September 2015
- Michalska, Marta; Wolf, Philipp
- Frontiers in Microbiology, Vol. 6
Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis
journal, August 2018
- Parkins, Michael D.; Somayaji, Ranjani; Waters, Valerie J.
- Clinical Microbiology Reviews, Vol. 31, Issue 4
The Assumptions Underlying the Analysis of Variance
journal, March 1947
- Eisenhart, Churchill
- Biometrics, Vol. 3, Issue 1
Interaction of Pseudomonas aeruginosa with epithelial cells: Identification of differentially regulated genes by expression microarray analysis of human cDNAs
journal, August 2000
- Ichikawa, J. K.; Norris, A.; Bangera, M. G.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 17
E-Selectin Ligands as Mechanosensitive Receptors on Neutrophils in Health and Disease
journal, January 2012
- Chase, S. D.; Magnani, J. L.; Simon, S. I.
- Annals of Biomedical Engineering, Vol. 40, Issue 4
Angiotensin II increases periostin expression via Ras/p38 MAPK/CREB and ERK1/2/TGF-β1 pathways in cardiac fibroblasts
journal, March 2011
- Li, Li; Fan, Dong; Wang, Cheng
- Cardiovascular Research, Vol. 91, Issue 1
Xenopus laevis FGF receptor substrate 3 (XFrs3) is important for eye development and mediates Pax6 expression in lens placode through its Shp2-binding sites
journal, January 2015
- Kim, Yeon-Jin; Bahn, Minjin; Hwan Kim, Yong
- Developmental Biology, Vol. 397, Issue 1
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
journal, November 2013
- Liao, Y.; Smyth, G. K.; Shi, W.
- Bioinformatics, Vol. 30, Issue 7
Pseudomonas aeruginosa Evasion of Phagocytosis Is Mediated by Loss of Swimming Motility and Is Independent of Flagellum Expression
journal, May 2010
- Amiel, Eyal; Lovewell, Rustin R.; O'Toole, George A.
- Infection and Immunity, Vol. 78, Issue 7
Pseudomonas aeruginosa Slime Glycolipoprotein Is a Potent Stimulant of Tumor Necrosis Factor Alpha Gene Expression and Activation of Transcription Activators Nuclear Factor κB and Activator Protein 1 in Human Monocytes
journal, August 2003
- Lagoumintzis, George; Christofidou, Myrto; Dimitracopoulos, George
- Infection and Immunity, Vol. 71, Issue 8
Protein kinase A catalytic subunit isoform PRKACA; History, function and physiology
journal, February 2016
- Turnham, Rigney E.; Scott, John D.
- Gene, Vol. 577, Issue 2
TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development
journal, November 2015
- Romberg, Neil; Virdee, Manmeet; Chamberlain, Nicolas
- Journal of Allergy and Clinical Immunology, Vol. 136, Issue 5
A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development
journal, October 2017
- Mao, Ai-Ping; Ishizuka, Isabel E.; Kasal, Darshan N.
- Nature Communications, Vol. 8, Issue 1
A comparison of normalization methods for high density oligonucleotide array data based on variance and bias
journal, January 2003
- Bolstad, B. M.; Irizarry, R. A.; Astrand, M.
- Bioinformatics, Vol. 19, Issue 2
Pseudomonas-Epithelial Cell Interactions Dissected With DNA Microarrays
journal, March 2002
- Lory, Stephen; Ichikawa, Jeffrey K.
- Chest, Vol. 121, Issue 3
Gene expression of TWIST1 and ZBTB16 is regulated by methylation modifications during the osteoblastic differentiation of mesenchymal stem cells: MAROFI et al.
journal, September 2018
- Marofi, Faroogh; Vahedi, Ghasem; Solali, Saeed
- Journal of Cellular Physiology, Vol. 234, Issue 5
Whole-genome RNAi screen highlights components of the endoplasmic reticulum/Golgi as a source of resistance to immunotoxin-mediated cytotoxicity
journal, February 2015
- Pasetto, Matteo; Antignani, Antonella; Ormanoglu, Pinar
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 10
Summaries of Affymetrix GeneChip probe level data
journal, February 2003
- Irizarry, R. A.
- Nucleic Acids Research, Vol. 31, Issue 4
Lack of Sphingosine Causes Susceptibility to Pulmonary Staphylococcus Aureus Infections in Cystic Fibrosis
journal, January 2016
- Tavakoli Tabazavareh, Shaghayegh; Seitz, Aaron; Jernigan, Peter
- Cellular Physiology and Biochemistry, Vol. 38, Issue 6
Genetic Adaptation of Pseudomonas aeruginosa to the Airways of Cystic Fibrosis Patients Is Catalyzed by Hypermutation
journal, October 2008
- Mena, A.; Smith, E. E.; Burns, J. L.
- Journal of Bacteriology, Vol. 190, Issue 24
RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1)
journal, June 2010
- Hyde, R. Katherine; Liu, P. Paul
- Journal of Cellular Biochemistry, Vol. 110, Issue 5
Community-Acquired Pneumonia Due to Gram-Negative Bacteria and Pseudomonas aeruginosa: Incidence, Risk, and Prognosis
journal, September 2002
- Arancibia, Francisco; Bauer, Torsten T.; Ewig, Santiago
- Archives of Internal Medicine, Vol. 162, Issue 16
Ceramide and sphingosine in pulmonary infections
journal, June 2015
- Seitz, Aaron P.; Grassmé, Heike; Edwards, Michael J.
- Biological Chemistry, Vol. 396, Issue 6-7
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
journal, November 2009
- Robinson, M. D.; McCarthy, D. J.; Smyth, G. K.
- Bioinformatics, Vol. 26, Issue 1
Expression profiling of genes regulated by sphingosine kinase1 signaling in a murine model of hyperoxia induced neonatal bronchopulmonary dysplasia
journal, August 2017
- Natarajan, Viswanathan; Ha, Alison W.; Dong, Yangbasai
- BMC Genomics, Vol. 18, Issue 1
Host Genetic Background Influences the Response to the Opportunistic Pseudomonas aeruginosa Infection Altering Cell-Mediated Immunity and Bacterial Replication
journal, September 2014
- De Simone, Maura; Spagnuolo, Lorenza; Lorè, Nicola Ivan
- PLoS ONE, Vol. 9, Issue 9
Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation
journal, January 2012
- McCarthy, Davis J.; Chen, Yunshun; Smyth, Gordon K.
- Nucleic Acids Research, Vol. 40, Issue 10
Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome
journal, February 2018
- Dortet, Laurent; Lombardi, Charlotte; Cretin, François
- Nature Microbiology, Vol. 3, Issue 3
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
journal, April 2003
- Irizarry, Rafael A.; Hobbs, Bridget; Collin, Francois
- Biostatistics, Vol. 4, Issue 2, p. 249-264
under dependency
journal, August 2001
- Yekutieli, Daniel; Benjamini, Yoav
- The Annals of Statistics, Vol. 29, Issue 4
Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity
journal, February 2018
- Koubi, Myriam; Poplineau, Mathilde; Vernerey, Julien
- Nucleic Acids Research, Vol. 46, Issue 7
Infection With Transmissible Strains of Pseudomonas aeruginosa and Clinical Outcomes in Adults With Cystic Fibrosis
journal, November 2010
- Aaron, Shawn D.; Vandemheen, Katherine L.; Ramotar, Karam
- JAMA, Vol. 304, Issue 19
Type 2 cGMP-dependent protein kinase regulates proliferation and differentiation in the colonic mucosa
journal, July 2012
- Wang, Rui; Kwon, In-Kiu; Thangaraju, Muthusamy
- American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 303, Issue 2
Positive Correlation between Virulence of Pseudomonas aeruginosa Mutants in Mice and Insects
journal, July 2000
- Jander, G.; Rahme, L. G.; Ausubel, F. M.
- Journal of Bacteriology, Vol. 182, Issue 13
ZBTB16 as a Downstream Target Gene of Osterix Regulates Osteoblastogenesis of Human Multipotent Mesenchymal Stromal Cells: ZBTB16 R EGULATES O STEOBLASTOGENESIS VIA O SX
journal, June 2016
- Onizuka, Satoru; Iwata, Takanori; Park, Sung-Joon
- Journal of Cellular Biochemistry, Vol. 117, Issue 10
Activation of the Epithelial Sodium Channel (ENaC) by the Alkaline Protease from Pseudomonas aeruginosa
journal, August 2012
- Butterworth, Michael B.; Zhang, Liang; Heidrich, Elisa M.
- Journal of Biological Chemistry, Vol. 287, Issue 39
Pseudomonas aeruginosa stimulates nuclear sphingosine-1-phosphate generation and epigenetic regulation of lung inflammatory injury
journal, February 2019
- Ebenezer, David L.; Berdyshev, Evgeny V.; Bronova, Irina A.
- Thorax, Vol. 74, Issue 6
Unique role of SNT-2/FRS2β/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways
journal, May 2006
- Huang, L.; Watanabe, M.; Chikamori, M.
- Oncogene, Vol. 25, Issue 49
Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo
journal, November 2008
- Szczepaniak, William S.; Zhang, Yingze; Hagerty, Sarah
- Translational Research, Vol. 152, Issue 5
Experiences building Globus Genomics: a next-generation sequencing analysis service using Galaxy, Globus, and Amazon Web Services: EXPERIENCES BUILDING GLOBUS GENOMICS
journal, April 2014
- Madduri, Ravi K.; Sulakhe, Dinanath; Lacinski, Lukasz
- Concurrency and Computation: Practice and Experience, Vol. 26, Issue 13
Characterization of cellular furin content as a potential factor determining the susceptibility of cultured human and animal cells to coronavirus infectious bronchitis virus infection
journal, November 2012
- Tay, Felicia P. L.; Huang, Mei; Wang, Li
- Virology, Vol. 433, Issue 2
Publisher Correction: A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development
journal, November 2017
- Mao, Ai-Ping; Ishizuka, Isabel E.; Kasal, Darshan N.
- Nature Communications, Vol. 8, Issue 1
Furin activates Pseudomonas exotoxin A by specific cleavage in vivo and in vitro.
journal, December 1994
- Inocencio, N. M.; Moehring, J. M.; Moehring, T. J.
- Journal of Biological Chemistry, Vol. 269, Issue 50
Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion
journal, January 2020
- Mathies, Tom; Mauldin, Richard E.
- Scientific Reports, Vol. 10, Issue 1
featureCounts: An efficient general-purpose program for assigning sequence reads to genomic features
text, January 2013
- Liao, Yang; Smyth, Gordon K.; Shi, Wei
- arXiv