دورية أكاديمية
Fatty acid metabolism of Mycobacterium tuberculosis : A double-edged sword.
| العنوان: | Fatty acid metabolism of Mycobacterium tuberculosis : A double-edged sword. |
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| المؤلفون: | Quinonez CG; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.; Department of Life Sciences, Faculty of Science and Technology, University of Westminster, London, W1W 6UV, United Kingdom., Lee JJ; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Lim J; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Odell M; School of Life Sciences, University of Lincoln, United Kingdom., Lawson CP; Stratclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom., Anyogu A; School of Biomedical Sciences, University of West London, London, United Kingdom., Raheem S; Department of Life Sciences, Faculty of Science and Technology, University of Westminster, London, W1W 6UV, United Kingdom., Eoh H; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. |
| المصدر: | Microbial cell (Graz, Austria) [Microb Cell] 2022 Feb 28; Vol. 9 (5), pp. 123-125. Date of Electronic Publication: 2022 Feb 28 (Print Publication: 2022). |
| نوع المنشور: | Journal Article; Comment |
| اللغة: | English |
| بيانات الدورية: | Publisher: Shared Science Publishers OG Country of Publication: Austria NLM ID: 101632887 Publication Model: eCollection Cited Medium: Print ISSN: 2311-2638 (Print) Linking ISSN: 23112638 NLM ISO Abbreviation: Microb Cell Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Graz : Shared Science Publishers OG, [2013]- |
| مستخلص: | 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. Competing Interests: Conflict of Interest: The authors declare no conflicts of interest. (Copyright: © 2022 Quinonez et al.) |
| التعليقات: | Comment on: mBio. 2022 Jan 11;:e0355921. (PMID: 35012349) |
| معلومات مُعتمدة: | R21 AI139386 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: drug tolerance; fatty acids; metabolomics; methylcitrate cycle; tuberculosis |
| تواريخ الأحداث: | Date Created: 20220601 Latest Revision: 20230615 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9113558 |
| DOI: | 10.15698/mic2022.05.777 |
| PMID: | 35647177 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2311-2638 |
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| DOI: | 10.15698/mic2022.05.777 |