ArticleMolecular microbiology2019
Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Article
- An adenylyl cyclase switch reroutes carbon from growth to virulence lipids inbioRxiv : the preprint server for biology · 2026Article
- A cloaked glutamate decarboxylase sustains the GABA shunt inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mycobacterium tuberculosis VadK is required for the regulation of the methylcitrate cycle and virulence.EMBO reports · 2026Article
- Article
- Pyruvate carboxylase is critical for biofilm formation in Mycobacterium tuberculosis.NPJ biofilms and microbiomes · 2026Article
- Article
- Article
- Accumulation of 2-methylcitrate induces metabolic imbalance inFrontiers in microbiology · 2026Article
- Whole Genome Sequencing and Metabolomic Profiling of Six Clinical Mycobacterium Tuberculosis Isolates Reveal Drug Resistance-Associated Features.Current microbiology · 2025Article
- Essential redundancies fuel Mycobacterium tuberculosis adaptation to the host.PLoS pathogens · 2025Review
- VadK, a Non-Canonical Kinase that Regulates the Methylcitrate Cycle and is Essential forbioRxiv : the preprint server for biology · 2025Article
- Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- The identification Mycobacterium tuberculosis genes that modulate long term survival in the presence of rifampicin and streptomycin.Scientific reports · 2025Article
- Metabolic Rewiring of Bacterial Pathogens in Response to Antibiotic Pressure-A Molecular Perspective.International journal of molecular sciences · 2025Review
- Itaconate mechanism of action and dissimilation inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- An integrated structural and biophysical approach to study carbon metabolism inQRB discovery · 2025Review
- Model systems to studyFrontiers in cellular and infection microbiology · 2025Review
- Aldehyde-based Activation of C2α-lactylthiamin Diphosphate Decarboxylation on Bacterial 1-deoxy-d-xylulose 5-phosphate Synthase.Chembiochem : a European journal of chemical biology · 2024Article
- Post-translational toxin modification by lactate controls Staphylococcus aureus virulence.Nature communications · 2024Article
6 more citing papers are in PubMed but not listed here.
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17 authors.
Funding
Abstract
Bacterial nutrition is an essential aspect of host-pathogen interaction. For the intracellular pathogen Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, fatty acids derived from lipid droplets are considered the major carbon source. However, many other soluble nutrients are available inside host cells and may be used as alternative carbon sources. Lactate and pyruvate are abundant in human cells and fluids, particularly during inflammation. In this work, we study Mtb metabolism of lactate and pyruvate combining classic microbial physiology with a 'multi-omics' approach consisting of transposon-directed insertion site sequencing (TraDIS), RNA-seq transcriptomics, proteomics and stable isotopic labelling coupled with mass spectrometry-based metabolomics. We discovered that Mtb is well adapted to use both lactate and pyruvate and that their metabolism requires gluconeogenesis, valine metabolism, the Krebs cycle, the GABA shunt, the glyoxylate shunt and the methylcitrate cycle. The last two pathways are traditionally associated with fatty acid metabolism and, unexpectedly, we found that in Mtb the methylcitrate cycle operates in reverse, to allow optimal metabolism of lactate and pyruvate. Our findings reveal a novel function for the methylcitrate cycle as a direct route for the biosynthesis of propionyl-CoA, the essential precursor for the biosynthesis of the odd-chain fatty acids.
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