1H NMR-based Metabolomic Profiling in Mice Infected with Mycobacterium tuberculosis
Open accessAbstract
Tuberculosis (TB) is one of three major infectious diseases, and the control of TB is becoming more difficult because of the emergence of multidrug-resistant and extensively drug-resistant strains. In this study, we explored the (1)H NMR-based metabolomics of TB using an aerobic TB infection model. Global profiling was applied to characterize the responses of C57Bl/6 mice to an aerobic infection with virulent Mycobacterium tuberculosis (MTB). The metabolic changes in organs (i.e., the lung, the target organ of TB, and the spleen and liver, remote systemic organs) and in serum from control and MTB-infected rats were investigated to clarify the host-pathogen interactions in MTB-infected host systems. Principal components analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots showed distinct separation between control and MTB-infected rats for all tissue and serum samples. Several tissue and serum metabolites were changed in MTB-infected rats, as compared to control rats. The precursors of membrane phospholipids, phosphocholine, and phosphoethanolamine, as well as glycolysis, amino acid metabolism, nucleotide metabolism, and the antioxidative stress response were altered based on the presence of MTB infection. This study suggests that NMR-based global metabolite profiling of organ tissues and serum could provide insight into the metabolic changes in host infected aerobically with virulent Mycobacterium tuberculosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Itaconate is an important immunomodulatory metabolite that negatively regulates the inflammatory response and cytokine production.
“Since 2016, several key studies have uncovered a role for itaconate as a crucial anti-inflammatory metabolite that negatively regulates the inflammatory response and cytokine production50,59–61, as shown in Figure 3.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [61]
High levels of succinate or 2-HG inhibit α-KGDDs, including PHDs, TET DNA demethylases, and JMJDs.
“High levels of succinate or 2-HG inhibit α-KGDDs. These include the PHDs, the TET DNA demethylases, and the JMJDs154-156”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [61]
Cites
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., et al. (1998) · Nature · doi:10.1038/31159 · Cited by 7,847 · see citing works
Orthogonal projections to latent structures (O‐PLS)
Trygg, J., & Wold, S. (2002) · Journal of Chemometrics · doi:10.1002/cem.695 · Cited by 2,489 · see citing works
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Sreekumar, A., Poisson, L., Rajendiran, T. M., Khan, A. P., Cao, Q., Yu, J., Laxman, B., Mehra, R., Lonigro, R. J., Li, Y., et al. (2009) · Nature · doi:10.1038/nature07762 · Cited by 2,238 · see citing works
Dieterle, F., Ross, A., Schlotterbeck, G., & Senn, H. (2006) · Analytical Chemistry · doi:10.1021/ac051632c · Cited by 1,772 · see citing works
Muñoz‐Elías, E. J., & McKinney, J. D. (2005) · Nature Medicine · doi:10.1038/nm1252 · Cited by 759 · see citing works
The glyoxylate cycle is required for fungal virulence
Lorenz, M. C., & Fink, G. R. (2001) · Nature · doi:10.1038/35083594 · Cited by 745 · see citing works
Zhuang, H., & Alavi, A. (2002) · Seminars in Nuclear Medicine · doi:10.1053/snuc.2002.29278 · Cited by 524 · see citing works
Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease
Rahman, I., & MacNee, W. (1999) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1999.277.6.l1067 · Cited by 420 · see citing works
Muñoz‐Elías, E. J., Upton, A. M., Cherian, J., & McKinney, J. D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05155.x · Cited by 360 · see citing works
The role of taurine in diabetes and the development of diabetic complications
Hansen, S. H. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.229 · Cited by 281 · see citing works
Conservation of the metabolomic response to starvation across two divergent microbes
Brauer, M. J., Yuan, J., Bennett, B. D., Lu, W., Kimball, E., Botstein, D., & Rabinowitz, J. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609508103 · Cited by 272 · see citing works
Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.
Sharma, V., Sharma, S., zu Bentrup, K. H., McKinney, J. D., Russell, D. G., Jacobs, W. R., & Sacchettini, J. C. (2000) · Nature Structural Biology · doi:10.1038/77964 · Cited by 250 · see citing works
Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum
Reyes, P., Rathod, P. K., Sanchez, D. J., et al. (1982) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(82)90035-4 · Cited by 221 · see citing works
Species Variation in the Fecal Metabolome Gives Insight into Differential Gastrointestinal Function
Saric, J., Wang, Y., Li, J., Coen, M., Utzinger, J., Marchesi, J. R., Keiser, J., Veselkov, K., Lindon, J. C., Nicholson, J. K., et al. (2007) · Journal of Proteome Research · doi:10.1021/pr070340k · Cited by 188 · see citing works
Macallan, D. C. (1999) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/s0732-8893(99)00007-3 · Cited by 188 · see citing works
Barak, A. J., Beckenhauer, H. C., Junnila, M., & Tuma, D. J. (1993) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1993.tb00798.x · Cited by 173 · see citing works
Paton, N. I., Chua, Y.-K., Earnest, A., & Chee, C. B.-E. (2004) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/80.2.460 · Cited by 155 · see citing works
Targeting Purine and Pyrimidine Metabolism in Human Apicomplexan Parasites
Hyde, J. (2006) · Current Drug Targets · doi:10.2174/138945007779315524 · Cited by 144 · see citing works
Tian, L., Shi, M. M., & Forman, H. J. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.9997 · Cited by 142 · see citing works
An Inflammatory Arthritis-Associated Metabolite Biomarker Pattern Revealed by 1 H NMR Spectroscopy
Weljie, A. M., Dowlatabadi, R., Miller, B. J., et al. (2007) · Journal of Proteome Research · doi:10.1021/pr070123j · Cited by 140 · see citing works
Nonezymatic formation of succinate in mitochondria under oxidative stress
Fedotcheva, N. I., Sokolov, A. P., & Kondrashova, M. N. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.02.012 · Cited by 137 · see citing works
Rahman, I., Antonicelli, F. D., & MacNee, W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.5088 · Cited by 135 · see citing works
Urata, Y., Yamamoto, H., Goto, S., Tsushima, H., 赤澤昭一, Yamashita, S., Nagataki, S., & Kondo, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15146 · Cited by 133 · see citing works
Purine Salvage Pathways in the Apicomplexan Parasite Toxoplasma gondii
Chaudhary, K., Darling, J. A., Fohl, L. M., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404232200 · Cited by 128 · see citing works
Global metabolic responses of mice to Trypanosoma brucei brucei infection
Wang, Y., Utzinger, J., Saric, J., Li, J. V., Burckhardt, J., Dirnhofer, S., Nicholson, J. K., Singer, B. H., Brun, R., & Holmes, E. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801777105 · Cited by 127 · see citing works
An exploratory chemometric study of 1H NMR spectra of table wines
Larsen, F. H., van den Berg, F. W. J., & Engelsen, S. B. (2006) · Journal of Chemometrics · doi:10.1002/cem.991 · Cited by 124 · see citing works
Tuberculosis, malnutrition and wasting
Schwenk, A., & Macallan, D. C. (2000) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200007000-00008 · Cited by 120 · see citing works
Phelps, D. T., Ferro, T. J., Higgins, P. J., et al. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.269.4.l551 · Cited by 116 · see citing works
Macallan, D. C., McNurlan, M. A., Kurpad, A. V., et al. (1998) · Clinical Science · doi:10.1042/cs0940321 · Cited by 110 · see citing works
Streptococcus pneumoniaeandStaphylococcus aureusPneumonia Induce Distinct Metabolic Responses
Slupsky, C. M., Cheypesh, A., Chao, D. V., Fu, H., Rankin, K. N., Marrie, T. J., & Lacy, P. (2009) · Journal of Proteome Research · doi:10.1021/pr900103y · Cited by 100 · see citing works
T cells in mycobacterial infection and disease
Cooper, A. M. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.06.004 · Cited by 98 · see citing works
Effects of Mainstream Cigarette Smoke on the Global Metabolome of Human Lung Epithelial Cells
Vulimiri, S. V., Misra, M., Hamm, J. T., et al. (2009) · Chemical Research in Toxicology · doi:10.1021/tx8003246 · Cited by 88 · see citing works
Erman, F., Balkan, J., Çevikbaş, U., Koçak‐Toker, N., & Uysal, M. (2004) · Amino Acids · doi:10.1007/s00726-004-0105-5 · Cited by 84 · see citing works
Sestili, P., Barbieri, E., Martinelli, C., Battistelli, M., Guescini, M., Vallorani, L., Casadei, L., D'Emilio, A., Falcieri, E., Piccoli, G., et al. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200800504 · Cited by 84 · see citing works
Jeon, B., Derrick, S. C., Lim, J., Kolibab, K., Dheenadhayalan, V., Yang, A. L., Kreiswirth, B. N., & Morris, S. L. (2008) · Infection and Immunity · doi:10.1128/iai.00019-08 · Cited by 77 · see citing works
Self-citationThe Pathway of Itaconate Metabolism by Liver Mitochondria
Wang, S., Adler, J., & Lardy, H. A. (1961) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64421-7 · Cited by 75 · see citing works
Kibadi, K., Boelaert, M., Fraga, A. G., Kayinua, M., Longatto‐Filho, A., Minuku, J.-B. M., Mputu-Yamba, J. B., Muyembé‐Tamfum, J., Pedrosa, J., Roux, J.-J., et al. (2010) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000736 · Cited by 75 · see citing works
Cellular metabolomics ofEscherchia coli
Rabinowitz, J. D. (2007) · Expert Review of Proteomics · doi:10.1586/14789450.4.2.187 · Cited by 72 · see citing works
Berg, I. A., Filatova, L. V., & Ivanovsky, R. N. (2002) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2002.tb11413.x · Cited by 71 · see citing works
Pinamonti, S., Muzzoli, M., Chicca, M. C., et al. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00030-5 · Cited by 70 · see citing works
Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery
Saric, J., Li, J. V., Wang, Y., Keiser, J., Bundy, J. G., Holmes, E. C., & Utzinger, J. (2008) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000254 · Cited by 69 · see citing works
Hillier, S., & Charnetzky, W. T. (1981) · Journal of Bacteriology · doi:10.1128/jb.145.1.452-458.1981 · Cited by 68 · see citing works
Li, J. V., Holmes, E. C., Saric, J., Keiser, J., Dirnhofer, S., Utzinger, J., & Wang, Y. (2008) · International Journal for Parasitology · doi:10.1016/j.ijpara.2008.10.010 · Cited by 65 · see citing works
Balkan, J., Parldar, F. H., lu, S. D. R.-A., et al. (2005) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200509000-00006 · Cited by 62 · see citing works
Simmonds, H. A., Duley, J. A., Fairbanks, L. D., et al. (1997) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005308923168 · Cited by 61 · see citing works
Daniel, J., Oh, T., Lee, C., & Kolattukudy, P. E. (2006) · Journal of Bacteriology · doi:10.1128/jb.01019-06 · Cited by 61 · see citing works
Hwang, G., Yang, J. K., Ryu, D. H., & Kwon, T. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00389.2009 · Cited by 58 · see citing works
Self-citationCho, S., Hazama, M., Urata, Y., et al. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00232-9 · Cited by 55 · see citing works
Self-citationYoung, J. F., Larsen, L. B., Malmendal, A., Nielsen, N. C., Straadt, I. K., Oksbjerg, N., & Bertram, H. C. (2010) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-7-9 · Cited by 54 · see citing works
Saric, J., Li, J. V., Wang, Y.-L., Keiser, J., Veselkov, K., Dirnhofer, S., Yap, I., Nicholson, J., Holmes, E., & Utzinger, J. (2009) · Journal of Proteome Research · doi:10.1021/pr900185s · Cited by 37 · see citing works
Serum amino acids in weight-losing patients with cancer and tuberculosis
Levin, L., Gevers, W., Jardine, L., Guel, F. J. M. D., & Duncan, E. J. (1983) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(83)90002-0 · Cited by 19 · see citing works
Impact of proteomics on anti-Mycobacterium tuberculosis (MTB) vaccine development.
Jagusztyn-Krynicka, E. K., Roszczenko, P., & Grabowska, A. D. (2009) · PubMed · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813 · see citing works
Krebs cycle Reborn in macrophage immunometabolism
Ryan, D. G., & O'Neill, L. A. J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081619-104850 · Cited by 444 · see citing works
Coupling Krebs cycle metabolites to signalling in immunity and cancer
Ryan, D. G., Murphy, M. P., Frezza, C., Prag, H. A., Chouchani, E. T., O’Neill, L. A., & Mills, E. L. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0014-7 · Cited by 398 · see citing works
Itaconic acid is a mammalian metabolite induced during macrophage activation
Strelko, C. L., Lu, W., Dufort, F. J., Seyfried, T. N., Chiles, T. C., Rabinowitz, J. D., & Roberts, M. F. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2070889 · Cited by 391 · see citing works
Németh, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., et al. (2016) · The FASEB Journal · doi:10.1096/fj.15-279398 · Cited by 136 · see citing works
Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense
Luan, H. H., & Medzhitov, R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.013 · Cited by 130 · see citing works
“Then in 2011, three groups described mammalian itaconate production in three separate immune-related contexts: in the lungs of Mycobacterium tuberculosis (MTB)-infectedmice (Shin et al., 2011), in the supernatant of LPS-treated macrophage-like RAW264.”
Background
- Authors
- Shin, J.-H., Yang, J.-Y., Jeon, B.-Y., Yoon, Y. J., Cho, S.-N., Kang, Y.-H., Ryu, D. H., & Hwang, G.-S.
- Affiliations
- Division of Bacterial Respiratory Infection, Center for Infectious Diseases, National Institute of Health, Centers for Disease Control and Prevention, Seoul 122-701, Republic of Korea
- Chungnam National University (KR)
- Yonsei University (KR)
- Korea Basic Science Institute (KR)
- Sungkyunkwan University (KR)
- Corresponding author
- Ryu, Do Hyun
- Hwang, Geum-Sook
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-04-14
- Volume
- 10
- Issue
- 5
- Pages
- 2238-2247
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2090707513
- Cited by
- 247
- References
- 52
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 28 · 2023: 11 · 2022: 11 · 2021: 21 · 2020: 29 · 2019: 24 · 2018: 15 · 2017: 11 · 2016: 14 · 2015: 16 · 2014: 15 · 2013: 12 · 2012: 7
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- tuberculosis, Mycobacterium tuberculosis, host-pathogen interaction, metabolite profiling, mouse infection model, serum metabolites, phospholipid precursors, phosphorylcholine, phosphoethanolamine, glycolysis, amino acid metabolism, nucleotide metabolism, oxidative stress response, multidrug-resistant tuberculosis
- MeSH terms
- Animals, Female, Lung, Mycobacterium tuberculosis, Magnetic Resonance Spectroscopy, Tuberculosis, Discriminant Analysis, Principal Component Analysis, Mice, Rats, Host-Pathogen Interactions, Metabolomics, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review