Fatty acid metabolism of Mycobacterium tuberculosis: A double-edged sword

Quinonez, CG, Lee, JJ, Lim, J , Odell, Mark, Lawson, CP, Anyogu, A, Raheem, S and Eoh, H (2022) Fatty acid metabolism of Mycobacterium tuberculosis: A double-edged sword. Microbial Cell, 9 (5). pp. 123-125. ISSN 2311-2638

Full content URL: https://www.doi.org/10.15698/mic2022.05.777

Fatty acid metabolism of Mycobacterium tuberculosis: A double-edged sword
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2022A-Quinonez-Microbial-Cell.pdf - Whole Document
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Unlike other heterotrophic bacteria, Mycobacterium tuberculosis (Mtb) can co-catabolize a range of carbon sources simultaneously. Evolution of Mtb within host nutrient environment allows Mtb to consume the host’s fatty acids as a main carbon source during infection. The fatty acid-induced metabolic advantage greatly contributes to Mtb’s pathogenicity and virulence. Thus, the identification of key enzymes involved in Mtb’s fatty acid metabolism is urgently needed to aid new drug development. Two fatty acid metabolism enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and isocitrate lyase (ICL) have been intensively studied as promising drug targets, but recently, Quinonez et al. (mBio, doi: 10.1128/mbio.03559-21) highlighted a link between the fatty acid-induced dormancy-like state and drug tolerance. Using metabolomics profiling of a PEPCK-deficient mutant, Quinonez et al. identified that over-accumulation of methylcitrate cycle (MCC) intermediates are phenotypically associated with enhanced drug tolerance against first- and second- line TB antibiotics. This finding was further corroborated by metabolomics and phenotypic characterization of Mtb mutants lacking either ICL or 2-methylcitrate dehydratase. Fatty acid metabolism induced drug-tolerance was also recapitulated in wildtype Mtb after treatment with authentic 2-methylisocitrate, an MCC intermediate. Together, the fatty acid-induced dormancy-like state and drug tolerance are attributed to dysregulated MCC activity.

Keywords:tuberculosis, metabolomics, drug tolerance, fatty acids, methylcitrate cycle
Subjects:C Biological Sciences > C730 Metabolic Biochemistry
C Biological Sciences > C521 Medical Microbiology
Divisions:College of Science > School of Life and Environmental Sciences > Department of Life Sciences
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ID Code:50904
Deposited On:12 Sep 2022 10:08

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