Document Detail


Intracellular Mycobacterium tuberculosis exploits host-derived fatty acids to limit metabolic stress.
MedLine Citation:
PMID:  23306194     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent data indicate that the nutrients available to Mycobacterium tuberculosis (Mtb) inside its host cell are restricted in their diversity. Fatty acids and cholesterol appear more favored; however, their degradation can result in certain metabolic stresses. Their breakdown can generate propionyl-CoA, which gives rise to potentially toxic intermediates. Detoxification of propionyl-CoA relies on the activity of the methylcitrate cycle, the methylmalonyl pathway, or incorporation of the propionyl-CoA into methyl-branched lipids in the cell wall. The current work explores carbon flux through these pathways, focusing primarily on those pathways responsible for the incorporation of propionyl-CoA into virulence-associated cell wall lipids. Exploiting both genetic and biochemical rescue, we demonstrate that these metabolic pressures are experienced by Mtb inside its host macrophage and that the bacterium accesses host fatty acid stores. The metabolism of these host lipids expands the acetyl-CoA pool and alleviates the pressure from propionyl-CoA. These data have major implications for our appreciation of central metabolism of Mtb during the course of infection.
Authors:
Wonsik Lee; Brian C VanderVen; Ruth J Fahey; David G Russell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-11     Completed Date:  2013-04-30     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6788-800     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetyl Coenzyme A / metabolism
Acyl Coenzyme A / metabolism
Animals
Bacterial Proteins / genetics,  metabolism
Cells, Cultured
Cholesterol / metabolism
Fatty Acids / metabolism*
Gene Expression Regulation, Bacterial
Host-Pathogen Interactions
Lipid Metabolism
Macrophages / cytology,  metabolism*,  microbiology
Mice
Mice, Inbred C57BL
Models, Biological
Mutation
Mycobacterium tuberculosis / genetics,  metabolism*,  physiology
Oxidation-Reduction
Stearic Acids / metabolism
Stress, Physiological*
Grant Support
ID/Acronym/Agency:
AI 067027/AI/NIAID NIH HHS; AI080651/AI/NIAID NIH HHS; HL055936/HL/NHLBI NIH HHS; R01 AI067027/AI/NIAID NIH HHS; R01 HL055936/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Bacterial Proteins; 0/Fatty Acids; 0/Stearic Acids; 317-66-8/propionyl-coenzyme A; 4ELV7Z65AP/stearic acid; 72-89-9/Acetyl Coenzyme A; 97C5T2UQ7J/Cholesterol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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