دورية أكاديمية

Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages.

التفاصيل البيبلوغرافية
العنوان: Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages.
المؤلفون: Cumming BM; Africa Health Research Institute, Durban, South Africa., Addicott KW; Africa Health Research Institute, Durban, South Africa., Adamson JH; Africa Health Research Institute, Durban, South Africa., Steyn AJ; Africa Health Research Institute, Durban, South Africa.; Department of Microbiology, Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, United States.
المصدر: ELife [Elife] 2018 Nov 16; Vol. 7. Date of Electronic Publication: 2018 Nov 16.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Host-Pathogen Interactions*, Citric Acid Cycle/*genetics , Fatty Acids/*metabolism , Glucose/*metabolism , Glycolysis/*genetics , Macrophages/*microbiology , Mycobacterium tuberculosis/*metabolism, Cell Differentiation/drug effects ; Cell Respiration ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Humans ; Macrophages/metabolism ; Metabolome ; Mitochondria/metabolism ; Mycobacterium bovis/growth & development ; Mycobacterium bovis/metabolism ; Mycobacterium tuberculosis/growth & development ; THP-1 Cells ; Tetradecanoylphorbol Acetate/pharmacology
مستخلص: How Mycobacterium tuberculosis ( Mtb ) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. Mtb infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, M. bovis BCG, or dead Mtb induced glycolytic phenotypes with greater flux. Furthermore, Mtb reduced the mitochondrial dependency on glucose and increased the mitochondrial dependency on fatty acids, shifting this dependency from endogenous fatty acids in uninfected cells to exogenous fatty acids in infected macrophages. We demonstrate how quantifiable bioenergetic parameters of the host can be used to accurately measure and track disease, which will enable rapid quantifiable assessment of drug and vaccine efficacy. Our findings uncover new paradigms for understanding the bioenergetic basis of host metabolic reprogramming by Mtb .
Competing Interests: BC, KA, JA, AS No competing interests declared
(© 2018, Cumming et al.)
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معلومات مُعتمدة: R21127182 United States NH NIH HHS; R01 AI111940 United States AI NIAID NIH HHS; R01AI111940 United States NH NIH HHS; R61 AI138280 United States AI NIAID NIH HHS; R61AI138280 United States NH NIH HHS
فهرسة مساهمة: Keywords: Mycobacterium bovis BCG; Mycobacterium tuberculosis; biochemistry; bioenergetic metabolism; chemical biology; extracellular flux analysis; human; infectious disease; macrophages; microbiology
المشرفين على المادة: 0 (Fatty Acids)
147336-22-9 (Green Fluorescent Proteins)
IY9XDZ35W2 (Glucose)
NI40JAQ945 (Tetradecanoylphorbol Acetate)
تواريخ الأحداث: Date Created: 20181117 Date Completed: 20190314 Latest Revision: 20200309
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC6286123
DOI: 10.7554/eLife.39169
PMID: 30444490
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.39169