BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.pdfhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.xpphttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.pnghttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.mhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1507180058?filename=MODEL1507180058.vcmlprimaryOK200Nicolas Le NovèreNon-curatedconstraint-based modelL3V1https://www.ebi.ac.uk/biomodels/MODEL150718005819356237falseBioModelsSBMLModelsRaghunathan2009 Genome scale metabolic network of Salmonella typhimurium (iRR1083)2009MODEL1507180058Non KineticRaghunathan A, Reed J, Shin S, Palsson B, Daefler SRaghunathan A19356237,
BACKGROUND: Infections with Salmonella cause significant morbidity and mortality worldwide. Replication of Salmonella typhimurium inside its host cell is a model system for studying the pathogenesis of intracellular bacterial infections. Genome-scale modeling of bacterial metabolic networks provides a powerful tool to identify and analyze pathways required for successful intracellular replication during host-pathogen interaction. RESULTS: We have developed and validated a genome-scale metabolic network of Salmonella typhimurium LT2 (iRR1083). This model accounts for 1,083 genes that encode proteins catalyzing 1,087 unique metabolic and transport reactions in the bacterium. We employed flux balance analysis and in silico gene essentiality analysis to investigate growth under a wide range of conditions that mimic in vitro and host cell environments. Gene expression profiling of S. typhimurium isolated from macrophage cell lines was used to constrain the model to predict metabolic pathways that are likely to be operational during infection. CONCLUSION: Our analysis suggests that there is a robust minimal set of metabolic pathways that is required for successful replication of Salmonella inside the host cell. This model also serves as platform for the integration of high-throughput data. Its computational power allows identification of networked metabolic pathways and generation of hypotheses about metabolism during infection, which might be used for the rational design of novel antibiotics or vaccine strains.. null, 3.
Department of Infectious Diseases, Mount Sinai School of Medicine, New York, USA.n.lenovere@gmail.comThe Babraham Institute<h4>Background</h4>Infections with Salmonella cause significant morbidity and mortality worldwide. Replication of Salmonella typhimurium inside its host cell is a model system for studying the pathogenesis of intracellular bacterial infections. Genome-scale modeling of bacterial metabolic networks provides a powerful tool to identify and analyze pathways required for successful intracellular replication during host-pathogen interaction.<h4>Results</h4>We have developed and validated a genome-scale metabolic network of Salmonella typhimurium LT2 (iRR1083). This model accounts for 1,083 genes that encode proteins catalyzing 1,087 unique metabolic and transport reactions in the bacterium. We employed flux balance analysis and in silico gene essentiality analysis to investigate growth under a wide range of conditions that mimic in vitro and host cell environments. Gene expression profiling of S. typhimurium isolated from macrophage cell lines was used to constrain the model to predict metabolic pathways that are likely to be operational during infection.<h4>Conclusion</h4>Our analysis suggests that there is a robust minimal set of metabolic pathways that is required for successful replication of Salmonella inside the host cell. This model also serves as platform for the integration of high-throughput data. Its computational power allows identification of networked metabolic pathways and generation of hypotheses about metabolism during infection, which might be used for the rational design of novel antibiotics or vaccine strains.Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction.Raghunathan Anu A, Reed Jennifer J, Shin Sookil S, Palsson Bernhard B, Daefler Simon S12, [5], Salmonella enterica subsp. enterica serovar 1, scale tissue, Salmonella choleraesuis serotype typhimurium, Salmonella typhi-murium, Salmonella enterica ser. typhimurium, Samonella typhimurium., scale, Salmonella enterica serovar Typhimurium, Genomes, Salmonella typhimurium, plant peltate hair, peltate hair, scale (sensu Metazoa), 2, 4, Salmonella enterica serotype Typhimurium, scales, Salmonella typhimurium LT2, Bacillus typhimurium, :i:1, 12:i:1, Salmonella enterica 1biochemical pathways, Metabolic Networks, Networks, scale tissue, IPP2A2, Metabolic Process, nucleocytoplasm, Materials, determination, antimicrobials, postnatal development, Metabolic Concepts, positive regulation by symbiont of host non-apoptotic programmed cell death, Infestations and Infections, antimicrobial agents, growth and development, protein, Pl, symbiotic process, Salmonella enterica subsp. enterica serovar Typhimurium strain LT2-LTL2, Case Fatality Rates, 12, 5730420M11Rik, Transcript Expression Analysis, dmTAF[[II]]230, Death Rates, solute:solute exchange, protein polypeptide chains, microbicides, macrophage, hemolysis by symbiont of host RBCs, Gene Expression Monitorings, pathogenesis, Concepts, 2, Strain., 4, encompassing mutualism through parasitism, Excess Mortalities, Analysis, Profilings, Metabolism Concept, protein aggregate, Phenomenon, antimicrobial, SET, modification by symbiont of host biological process, Salmonella enterica serovar Typhimurium, stimulation by symbiont of host programmed cell death, TFIID TAF250, Genomes, Analyses, Crude Mortality Rates, cel, TAF-I, catabolism, plant peltate hair, Antibiotika, phosphatase 2A inhibitor I2PP2A, Pathways, proteins, metabolic process resulting in cell growth, activation by organism of programmed cell death in other organism during symbiotic interaction, DmelCG4299, [5], Gene Expression Analysis, set, IGAAD, DmelCG10574, CFR Case Fatality Rate, biotransformation, Infections and Infestations, Strains, cytolysis by organism of host cells, Age-Specific Death Rate, podocyte, Catabolism, intracellular, antibiotic, phapii, symbiotic interaction between organisms, dTAF[[II]]230, Pathway, wide/broad, Process, typical plasmatocyte, metabolism resulting in cell growth, Crude Death, Monitorings, TAF200, StF-IT-1, Metabolic Network, TAFII-250, monocyte-derived macrophage, TAF250/230, positive regulation by symbiont of host programmed cell death, results, Crude Mortality, Gene Expression, TAFII250, Mortality, enhancement of host programmed cell death, single-organism transport, modulation by symbiont of host system process, Genetic Materials, secretion, microbicide, internal to cell, Genetic Material, haemolysis in host, Salmonella enterica subsp. enterica serovar Typhimurium strain LT2, HLA-DR-associated protein II, death rate, growth pattern, DI-2, non-developmental growth, Transcriptome Profilings, Bacterial Diseases, I-2Dm, perturbation by symbiont of host defense response, Mortalities, Infection and Infestation, INSDC_feature:gene, CG4299, inhibitor of granzyme A-activated DNase, CG17603, TAF[[II]], induction by organism of programmed cell death in other organism during symbiotic interaction, modification by symbiont of host morphology or physiology, organ system, I-2PP1, regulation of cytolysis of host cells by symbiont, wide, Mortality Rate, Crude Death Rate, Gene Expression Analyses, TAF-IBETA, induction by symbiont of host programmed cell death, Taf250, hemolysis by symbiont of host red blood cells, Material, SR3-5, activation by symbiont of host programmed cell death, small molecule transport, Cistron, Expression Analysis, TAF-Ibeta, histiocyte, Mortality Determinant, i2pp2a, Strains and Sprains, :i:1, TAF230, 12:i:1, d230, Bacterial Disease, Salmonella typhi-murium, parasitism, Samonella, antibiotique, Processes, Mortality Declines, regulation by symbiont of host system process, modulation by organism of defense response of other organism involved in symbiotic interaction, peltate hair, Excess, Gene, Bacterial Infections, commensalism, dTAFII250, Network, Crude Mortality Rate, broad, Metabolic Processes, protein-containing complex, mortality measurement, EfW1, body system, PHAPII, Age-Specific Death, Gene Expression Profilings, Mortality Determinants, Crude, mRNA Differential Displays, Rate, Determinant, Gene Expression Pattern Analysis, polypeptide chain, template-activating factor I, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, dmTAF1, Taf230, Metabolism, symbiotic interaction between species, Gene Products, Case Fatality, system, symbiosis, agranular plasmatocyte, Metabolism Phenomena, Sprains, Bacillus typhimurium, antibiotics, upregulation by symbiont of host programmed cell death, TAF250, protoplasm, Differential Mortality, induction of non-apoptotic programmed cell death by other organism, Taf200, Excess Mortality, anatomical systems, Bacterial Infection, symbiotic interaction between host and organism, dTAF[[II]]250, Genetic, protoplast, Infections, cell, ipp2a2, 2pp2a, Metabolic Concept, Transcriptomics, Taf1p, Transcript Expression, Transcriptome Analysis, Age-Specific, CG10574, Monitoring, dTAF250, Infestation and Infection, 2PP2A, lamellocyte, taf-ibeta, Mortality Rates, mortality rate, Crude Death Rates, dSET, dSet, scale (sensu Metazoa), Expression Analyses, TAF, Age Specific Death Rate, Antibiotikum, Morbidities, macrophagocyte, Profiling, Salmonella choleraesuis serotype typhimurium, data, TAF[[II]]250, disruption by symbiont of host cell, activation by organism of non-apoptotic programmed cell death in other organism, Transcriptome, Mortality Decline, hemolysin activity, degradation, protein complex, Salmonella typhimurium, Samonella typhimurium, Proteins, Sprain, igaad, l(3)84Ab, BG:DS00004.13, Cistrons, Cell, dTAF230, Concept, Metabolic Phenomena, development, Differential Display, transcription profiling, Case Fatality Rate, Metabolism Concepts, Transcript Expression Analyses, survival, native protein, natural protein, I-2PP2A, p230, Protein, chemical analysis, Dm I-2, I2PP2A, Phenomena, Infection, modulation by symbiont of host defense response, TAF[[II]]250/230, TFIID, Salmonella enterica serotype Typhimurium, background, connected anatomical system, induction by organism of programmed cell death in other organism involved in symbiotic interaction, mitigation by symbiont of host defense response, scales, Determinants, Death, mRNA Differential Display, metabolism, gene expression profiling, Metabolic Pathways, Metabolic Phenomenon, Salmonella enterica 1, Bacterial, Taf[[II]]250, Rates, Gene Expression Monitoring, Death Rate, multicellular organism metabolic process, enhancement of host programmed cell death by organism, TAF[[II]]230, Salmonella enterica ser. typhimurium, scale, Transcriptome Profiling, biodegradation, mRNA, Metabolic, symbiotic interaction, postnatal growth, TAF[II]250, Differential Displays, Age-Specific Death Rates, Transcriptome Analyses, introduction, host-pathogen interaction, Protein Gene Products, Salmonella enterica subsp. enterica serovar Typhimurium LT2, Gene Proteins, Salmonella enterica subsp. enterica serovar 1, dSET/TAF-Ibeta, Differential, 2610030F17Rik, single-organism metabolic process, activation by organism of host programmed cell death, DmelCG17603, Vaccine, Decline, granulocyte, Metabolic Pathway, assay, Salmonella typhimurium LT2, AA407739, growth, Differential Mortalities, TAF1, Anabolismbiochemical pathways, extent, host organism, scale tissue, IPP2A2, Metabolic Process, nucleocytoplasm, Materials, Public Sectors, determination, antimicrobials, postnatal development, Metabolic Concepts, positive regulation by symbiont of host non-apoptotic programmed cell death, Infestations and Infections, antimicrobial agents, growth and development, protein, Pl, symbiotic process, Salmonella enterica subsp. enterica serovar Typhimurium strain LT2-LTL2, 12, Case Fatality Rates, 5730420M11Rik, dmTAF[[II]]230, Transcript Expression Analysis, Death Rates, solute:solute exchange, protein polypeptide chains, microbicides, macrophage, hemolysis by symbiont of host RBCs, Gene Expression Monitorings, Line, pathogenesis, Concepts, 2, 4, encompassing mutualism through parasitism, Excess Mortalities, Analysis, Profilings, Metabolism Concept, Public Enterprise, protein aggregate, Phenomenon, antimicrobial, SET, modification by symbiont of host biological process, Salmonella enterica serovar Typhimurium, stimulation by symbiont of host programmed cell death, TFIID TAF250, Genomes, Analyses, Crude Mortality Rates, cel, TAF-I, catabolism, plant peltate hair, Antibiotika, phosphatase 2A inhibitor I2PP2A, Public Domains, proteins, metabolic process resulting in cell growth, activation by organism of programmed cell death in other organism during symbiotic interaction, DmelCG4299, [5], Gene Expression Analysis, set, IGAAD, DmelCG10574, CFR Case Fatality Rate, biotransformation, Infections and Infestations, Strains, cytolysis by organism of host cells, Age-Specific Death Rate, podocyte, Catabolism, intracellular, antibiotic, phapii, symbiotic interaction between organisms, dTAF[[II]]230, wide/broad, Process, completeness, typical plasmatocyte, metabolism resulting in cell growth, Crude Death, TAF200, Monitorings, StF-IT-1, TAFII-250, TAF250/230, monocyte-derived macrophage, positive regulation by symbiont of host programmed cell death, results, Crude Mortality, Gene Expression, TAFII250, Mortality, enhancement of host programmed cell death, single-organism transport, Public Domain, modulation by symbiont of host system process, Domains, Genetic Materials, secretion, microbicide, internal to cell, Genetic Material, Domain, haemolysis in host, Lines, Salmonella enterica subsp. enterica serovar Typhimurium strain LT2, HLA-DR-associated protein II, death rate, growth pattern, DI-2, non-developmental growth, Transcriptome Profilings, Bacterial Diseases, I-2Dm, perturbation by symbiont of host defense response, Mortalities, Infection and Infestation, INSDC_feature:gene, CG4299, inhibitor of granzyme A-activated DNase, CG17603, TAF[[II]], induction by organism of programmed cell death in other organism during symbiotic interaction, modification by symbiont of host morphology or physiology, organ system, I-2PP1, regulation of cytolysis of host cells by symbiont, wide, Mortality Rate, Crude Death Rate, Sector, Gene Expression Analyses, TAF-IBETA, induction by symbiont of host programmed cell death, Taf250, hemolysis by symbiont of host red blood cells, Material, SR3-5, activation by symbiont of host programmed cell death, small molecule transport, Cistron, Expression Analysis, TAF-Ibeta, histiocyte, Mortality Determinant, i2pp2a, Strains and Sprains, :i:1, TAF230, 12:i:1, d230, Sectors, Bacterial Disease, Salmonella typhi-murium, parasitism, Samonella, antibiotique, Processes, Mortality Declines, regulation by symbiont of host system process, peltate hair, modulation by organism of defense response of other organism involved in symbiotic interaction, number, Excess, Gene, commensalism, Bacterial Infections, dTAFII250, Copyrights, Crude Mortality Rate, broad, Metabolic Processes, protein-containing complex, mortality measurement, EfW1, body system, presence, PHAPII, Age-Specific Death, Gene Expression Profilings, Mortality Determinants, Crude, mRNA Differential Displays, Rate, Determinant, Gene Expression Pattern Analysis, polypeptide chain, template-activating factor I, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, dmTAF1, Taf230, Metabolism, symbiotic interaction between species, Gene Products, Case Fatality, system, symbiosis, agranular plasmatocyte, Metabolism Phenomena, Sprains, Enterprises, Bacillus typhimurium, antibiotics, upregulation by symbiont of host programmed cell death, TAF250, protoplasm, Differential Mortality, induction of non-apoptotic programmed cell death by other organism, Taf200, symbiotic interaction between host and organism, Excess Mortality, anatomical systems, Bacterial Infection, dTAF[[II]]250, Genetic, protoplast, Infections, cell, ipp2a2, 2pp2a, Metabolic Concept, Taf1p, Transcriptomics, Transcript Expression, Transcriptome Analysis, Age-Specific, Public Enterprises, CG10574, Monitoring, dTAF250, Infestation and Infection, Abstract, 2PP2A, lamellocyte, taf-ibeta, Mortality Rates, mortality rate, Crude Death Rates, dSET, dSet, scale (sensu Metazoa), TAF, Expression Analyses, Enterprise, Age Specific Death Rate, Antibiotikum, Morbidities, macrophagocyte, Profiling, Salmonella choleraesuis serotype typhimurium, data, TAF[[II]]250, disruption by symbiont of host cell, activation by organism of non-apoptotic programmed cell death in other organism, Transcriptome, Mortality Decline, hemolysin activity, degradation, protein complex, Salmonella typhimurium, Samonella typhimurium, Proteins, Sprain, igaad, Cell Lines, l(3)84Ab, BG:DS00004.13, Cistrons, Cell, dTAF230, Concept, Metabolic Phenomena, development, Differential Display, transcription profiling, Case Fatality Rate, Metabolism Concepts, count in organism, Transcript Expression Analyses, survival, native protein, natural protein, I-2PP2A, Public, p230, chemical analysis, Protein, Dm I-2, I2PP2A, Phenomena, Strain, Infection, modulation by symbiont of host defense response, TAF[[II]]250/230, TFIID, Salmonella enterica serotype Typhimurium, background, scales, connected anatomical system, induction by organism of programmed cell death in other organism involved in symbiotic interaction, mitigation by symbiont of host defense response, Determinants, Death, mRNA Differential Display, metabolism, gene expression profiling, Data Base, Metabolic Phenomenon, Salmonella enterica 1, Bacterial, Taf[[II]]250, Rates, Gene Expression Monitoring, Death Rate, multicellular organism metabolic process, enhancement of host programmed cell death by organism, TAF[[II]]230, Salmonella enterica ser. typhimurium, scale, Transcriptome Profiling, biodegradation, mRNA, Metabolic, symbiotic interaction, postnatal growth, TAF[II]250, Differential Displays, Age-Specific Death Rates, Transcriptome Analyses, introduction, host-pathogen interaction, Protein Gene Products, Salmonella enterica subsp. enterica serovar Typhimurium LT2, Gene Proteins, Salmonella enterica subsp. enterica serovar 1, dSET/TAF-Ibeta, Differential, 2610030F17Rik, single-organism metabolic process, activation by organism of host programmed cell death, DmelCG17603, Vaccine, Decline, granulocyte, Public., assay, quantitative, Salmonella typhimurium LT2, AA407739, growth, Differential Mortalities, TAF1, Anabolism, presence or absence in organismSalmonella choleraesuis serotype typhimurium, symbiotic interaction between organisms, symbiotic interaction between host and organism, Salmonella typhi-murium, Salmonella enterica ser. typhimurium, parasitism, Salmonella enterica serovar Typhimurium, determination, Salmonella typhimurium, symbiotic interaction, Samonella typhimurium, commensalism, symbiotic process, host-pathogen interaction, 12, [5], Salmonella enterica subsp. enterica serovar 1, symbiotic interaction between species., chemical analysis, 2, 4, encompassing mutualism through parasitism, assay, Salmonella enterica serotype Typhimurium, symbiosis, Salmonella typhimurium LT2, Bacillus typhimurium, :i:1, 12:i:1, Salmonella enterica 1falseRaghunathan2009 - Genome-scale metabolic network of Salmonella typhimurium (iRR1083)
Raghunathan2009 - Genome-scale metabolic
network of Salmonella typhimurium (iRR1083)
This model is described in the article:
Constraint-based analysis of
metabolic capacity of Salmonella typhimurium during
host-pathogen interaction.
Raghunathan A, Reed J, Shin S,
Palsson B, Daefler S.
BMC Syst Biol 2009; 3: 38
Abstract:
BACKGROUND: Infections with Salmonella cause significant
morbidity and mortality worldwide. Replication of Salmonella
typhimurium inside its host cell is a model system for studying
the pathogenesis of intracellular bacterial infections.
Genome-scale modeling of bacterial metabolic networks provides
a powerful tool to identify and analyze pathways required for
successful intracellular replication during host-pathogen
interaction. RESULTS: We have developed and validated a
genome-scale metabolic network of Salmonella typhimurium LT2
(iRR1083). This model accounts for 1,083 genes that encode
proteins catalyzing 1,087 unique metabolic and transport
reactions in the bacterium. We employed flux balance analysis
and in silico gene essentiality analysis to investigate growth
under a wide range of conditions that mimic in vitro and host
cell environments. Gene expression profiling of S. typhimurium
isolated from macrophage cell lines was used to constrain the
model to predict metabolic pathways that are likely to be
operational during infection. CONCLUSION: Our analysis suggests
that there is a robust minimal set of metabolic pathways that
is required for successful replication of Salmonella inside the
host cell. This model also serves as platform for the
integration of high-throughput data. Its computational power
allows identification of networked metabolic pathways and
generation of hypotheses about metabolism during infection,
which might be used for the rational design of novel
antibiotics or vaccine strains.
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2015-07-282015-07-302015-07-18MODEL150718005819356237MODEL1507180058