ArticleCell chemical biology2017
Fumarase Deficiency Causes Protein and Metabolite Succination and Intoxicates Mycobacterium tuberculosis.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Mycobacterial cell division arrest and smooth-to-rough envelope transition using CRISPRi-mediated genetic repression systems.FEBS open bio · 2026Article
- A Key Metabolic Protein in Active Mycobacterium tuberculosis: Insights into Carbon, Nitrogen, and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- Regulation of airway fumarate by host and pathogen promotes Staphylococcus aureus pneumonia.Nature communications · 2025Article
- Regulation of airway fumarate by host and pathogen promotesbioRxiv : the preprint server for biology · 2025Article
- Rapid and Efficient Synthesis of Succinated Thiol Compounds via Maleic Anhydride Derivatization.Molecules (Basel, Switzerland) · 2025Article
- Combined inactivation of the SOS response with TCA fumarases and the adaptive response enhances antibiotic susceptibility againstFrontiers in microbiology · 2025Article
- Combination of gallium citrate and levofloxacin induces a distinct metabolome profile and enhances growth inhibition of multidrug-resistantFrontiers in microbiology · 2024Article
- Multifaceted mitochondria in innate immunity.npj metabolic health and disease · 2024Review
- Cysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression preventsScience advances · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- HEmerging microbes & infections · 2022Article
- Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides.International journal of molecular sciences · 2022Article
- The role of immunomodulatory metabolites in shaping the inflammatory response of macrophages.BMB reports · 2022Review
- Article
- Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum.The Journal of biological chemistry · 2022Article
- Deciphering functional redundancy and energetics of malate oxidation in mycobacteria.The Journal of biological chemistry · 2022Article
- Pyruvate Supports RET-Dependent Mitochondrial ROS Production to ControlFrontiers in immunology · 2022Article
- Dimethyl fumarate eliminates differentially culturableFrontiers in cellular and infection microbiology · 2022Article
- Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Macrophage metabolic reprogramming during chronic lung disease.Mucosal immunology · 2021Review
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10 authors at 3 institutions in 1 country.
Funding
Abstract
Enzymes of central carbon metabolism are essential mediators of Mycobacterium tuberculosis (Mtb) physiology and pathogenicity, but are often perceived to lack sufficient species selectivity to be pursued as potential drug targets. Fumarase (Fum) is an enzyme of the canonical tricarboxylic acid cycle and is dispensable in many organisms. Transposon mutagenesis studies in Mtb, however, indicate that Fum is required for optimal growth. Here, we report the generation and characterization of a genetically engineered Mtb strain in which Fum expression is conditionally regulated. This revealed that Fum deficiency is bactericidal in vitro and during both the acute and chronic phases of mouse infection. This essentiality is linked to marked accumulations of fumarate resulting in protein and metabolite succination, a covalent modification of cysteine thiol residues. These results identify Mtb Fum as a potentially species-specific drug target whose inactivation may kill Mtb through a covalently irreversible form of metabolic toxicity.
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