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Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study.
Frediani, Jennifer K; Jones, Dean P; Tukvadze, Nestan; Uppal, Karan; Sanikidze, Eka; Kipiani, Maia; Tran, ViLinh T; Hebbar, Gautam; Walker, Douglas I; Kempker, Russell R; Kurani, Shaheen S; Colas, Romain A; Dalli, Jesmond; Tangpricha, Vin; Serhan, Charles N; Blumberg, Henry M; Ziegler, Thomas R.
Afiliação
  • Frediani JK; Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, Georgia, United States of America; Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, United States of America; D
  • Jones DP; Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, Georgia, United States of America; Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, United States of America; D
  • Tukvadze N; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.
  • Uppal K; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Sanikidze E; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.
  • Kipiani M; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.
  • Tran VT; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Hebbar G; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Walker DI; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America; Department of Civil and Environmental Engineering, Tufts University, Medford, Massachusetts, United States of America.
  • Kempker RR; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Kurani SS; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
  • Colas RA; Center for Experimental Therapeutics and Reperfusion Injury, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Dalli J; Center for Experimental Therapeutics and Reperfusion Injury, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Tangpricha V; Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, Georgia, United States of America; Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, United States of America; D
  • Serhan CN; Center for Experimental Therapeutics and Reperfusion Injury, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Blumberg HM; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
  • Ziegler TR; Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, Georgia, United States of America; Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia, United States of America; D
PLoS One ; 9(10): e108854, 2014.
Article em En | MEDLINE | ID: mdl-25329995
We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose Pulmonar / Metabolômica / Mycobacterium tuberculosis Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose Pulmonar / Metabolômica / Mycobacterium tuberculosis Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article