Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection
Metabolic adaptation to the host cell is important for obligate intracellular pathogens such as Chlamydia trachomatis (Ct). Here we infer the flux differences for Ct from proteome and qRT-PCR data by comprehensive pathway modeling. We compare the comparatively inert infectious elementary body (EB) a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02350/full |
| _version_ | 1811293858193997824 |
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| author | Manli Yang Karthika Rajeeve Karthika Rajeeve Thomas Rudel Thomas Dandekar Thomas Dandekar |
| author_facet | Manli Yang Karthika Rajeeve Karthika Rajeeve Thomas Rudel Thomas Dandekar Thomas Dandekar |
| author_sort | Manli Yang |
| collection | DOAJ |
| description | Metabolic adaptation to the host cell is important for obligate intracellular pathogens such as Chlamydia trachomatis (Ct). Here we infer the flux differences for Ct from proteome and qRT-PCR data by comprehensive pathway modeling. We compare the comparatively inert infectious elementary body (EB) and the active replicative reticulate body (RB) systematically using a genome-scale metabolic model with 321 metabolites and 277 reactions. This did yield 84 extreme pathways based on a published proteomics dataset at three different time points of infection. Validation of predictions was done by quantitative RT-PCR of enzyme mRNA expression at three time points. Ct’s major active pathways are glycolysis, gluconeogenesis, glycerol-phospholipid (GPL) biosynthesis (support from host acetyl-CoA) and pentose phosphate pathway (PPP), while its incomplete TCA and fatty acid biosynthesis are less active. The modeled metabolic pathways are much more active in RB than in EB. Our in silico model suggests that EB and RB utilize folate to generate NAD(P)H using independent pathways. The only low metabolic flux inferred for EB involves mainly carbohydrate metabolism. RB utilizes energy -rich compounds to generate ATP in nucleic acid metabolism. Validation data for the modeling include proteomics experiments (model basis) as well as qRT-PCR confirmation of selected metabolic enzyme mRNA expression differences. The metabolic modeling is made fully available here. Its detailed insights and models on Ct metabolic adaptations during infection are a useful modeling basis for future studies. |
| first_indexed | 2024-04-13T05:07:48Z |
| format | Article |
| id | doaj.art-f7c37f38d8e14d7bb2d4010018486d8b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T05:07:48Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f7c37f38d8e14d7bb2d4010018486d8b2022-12-22T03:01:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-10-011010.3389/fmicb.2019.02350484702Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During InfectionManli Yang0Karthika Rajeeve1Karthika Rajeeve2Thomas Rudel3Thomas Dandekar4Thomas Dandekar5Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, GermanyDepartment of Microbiology, Biocenter, University of Würzburg, Würzburg, GermanyDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Microbiology, Biocenter, University of Würzburg, Würzburg, GermanyDepartment of Bioinformatics, Biocenter, University of Würzburg, Würzburg, GermanyEuropean Molecular Biology Laboratory, Computational Biology and Structures Program, Heidelberg, GermanyMetabolic adaptation to the host cell is important for obligate intracellular pathogens such as Chlamydia trachomatis (Ct). Here we infer the flux differences for Ct from proteome and qRT-PCR data by comprehensive pathway modeling. We compare the comparatively inert infectious elementary body (EB) and the active replicative reticulate body (RB) systematically using a genome-scale metabolic model with 321 metabolites and 277 reactions. This did yield 84 extreme pathways based on a published proteomics dataset at three different time points of infection. Validation of predictions was done by quantitative RT-PCR of enzyme mRNA expression at three time points. Ct’s major active pathways are glycolysis, gluconeogenesis, glycerol-phospholipid (GPL) biosynthesis (support from host acetyl-CoA) and pentose phosphate pathway (PPP), while its incomplete TCA and fatty acid biosynthesis are less active. The modeled metabolic pathways are much more active in RB than in EB. Our in silico model suggests that EB and RB utilize folate to generate NAD(P)H using independent pathways. The only low metabolic flux inferred for EB involves mainly carbohydrate metabolism. RB utilizes energy -rich compounds to generate ATP in nucleic acid metabolism. Validation data for the modeling include proteomics experiments (model basis) as well as qRT-PCR confirmation of selected metabolic enzyme mRNA expression differences. The metabolic modeling is made fully available here. Its detailed insights and models on Ct metabolic adaptations during infection are a useful modeling basis for future studies.https://www.frontiersin.org/article/10.3389/fmicb.2019.02350/fullChlamydia trachomatismetabolic modelingmetabolic fluxinfection biologyelementary bodyreticulate body |
| spellingShingle | Manli Yang Karthika Rajeeve Karthika Rajeeve Thomas Rudel Thomas Dandekar Thomas Dandekar Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection Frontiers in Microbiology Chlamydia trachomatis metabolic modeling metabolic flux infection biology elementary body reticulate body |
| title | Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection |
| title_full | Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection |
| title_fullStr | Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection |
| title_full_unstemmed | Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection |
| title_short | Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection |
| title_sort | comprehensive flux modeling of chlamydia trachomatis proteome and qrt pcr data indicate biphasic metabolic differences between elementary bodies and reticulate bodies during infection |
| topic | Chlamydia trachomatis metabolic modeling metabolic flux infection biology elementary body reticulate body |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02350/full |
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