ArticleProceedings of the National Academy of Sciences of the United States of America2014
Methylcitrate cycle defines the bactericidal essentiality of isocitrate lyase for survival of Mycobacterium tuberculosis on fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed.
- Carbonic Anhydrases in Mycobacteria: Linking Metabolic Adaptation to Phenotypic Drug Tolerance.Current microbiology · 2026Review
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- An adenylyl cyclase switch reroutes carbon from growth to virulence lipids inbioRxiv : the preprint server for biology · 2026Article
- Mycobacterium tuberculosis VadK is required for the regulation of the methylcitrate cycle and virulence.EMBO reports · 2026Article
- Article
- The metallophosphoesterase Rv0805 regulates carbon flux and cell envelope homeostasis during growth of mycobacteria in propionate.Journal of bacteriology · 2026Article
- Exploring the Protein Landscape of Dormant Mycobacterium tuberculosis Through In Vitro Functional Studies.Advances in experimental medicine and biology · 2026Review
- A Key Metabolic Protein in Active Mycobacterium tuberculosis: Insights into Carbon, Nitrogen, and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- Different transcriptional regulatory activities of Mycobacterium bovis and Mycobacterium tuberculosis PhoPR systems.Access microbiology · 2026Article
- Cobamide metabolism, regulation, and adaptation inJournal of bacteriology · 2025Review
- VadK, a Non-Canonical Kinase that Regulates the Methylcitrate Cycle and is Essential forbioRxiv : the preprint server for biology · 2025Article
- Isoleucyl-tRNA synthetase depletion reveals vulnerabilities in Mycobacterium abscessus and Mycobacterium marinum.Communications biology · 2025Article
- Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Lipid Levels and Atherogenic Indices as Important Predictive Parameters in the Assessment of Cardiovascular Risk in Patients with Pulmonary Tuberculosis-Slovak Pilot Study.Medicina (Kaunas, Lithuania) · 2025Article
- Itaconate mechanism of action and dissimilation inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effect of TetR Family Transcriptional Regulator PccD on Phytosterol Metabolism ofMicroorganisms · 2024Article
- Loss of glycerol catabolism confers carbon-source-dependent artemisinin resistance inAntimicrobial agents and chemotherapy · 2024Article
- Propionate prevents loss of the PDIM virulence lipid in Mycobacterium tuberculosis.Nature microbiology · 2024Article
- TargetingMicrobiology (Reading, England) · 2024Review
- Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution.Nature communications · 2024Article
41 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
Few mutations attenuate Mycobacterium tuberculosis (Mtb) more profoundly than deletion of its isocitrate lyases (ICLs). However, the basis for this attenuation remains incompletely defined. Mtb's ICLs are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids. Here, we report that Mtb's ICLs are essential for survival on both acetate and propionate because of its methylisocitrate lyase (MCL) activity. Lack of MCL activity converts Mtb's methylcitrate cycle into a "dead end" pathway that sequesters tricarboxylic acid (TCA) cycle intermediates into methylcitrate cycle intermediates, depletes gluconeogenic precursors, and results in defects of membrane potential and intrabacterial pH. Activation of an alternative vitamin B12-dependent pathway of propionate metabolism led to selective corrections of TCA cycle activity, membrane potential, and intrabacterial pH that specifically restored survival, but not growth, of ICL-deficient Mtb metabolizing acetate or propionate. These results thus resolve the biochemical basis of essentiality for Mtb's ICLs and survival on fatty acids.
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