ArticleNature communications2019
Derailing the aspartate pathway of Mycobacterium tuberculosis to eradicate persistent infection.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Isotopic tracing inVirulence · 2026Article
- The Homoserine DehydrogenaseMicroorganisms · 2026Article
- Metabolic insights into the pathophysiology of tuberculous meningitis in FFPE postmortem human brain tissue.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Induced alanine auxotrophy as a therapeutic strategy against Mycobacterium tuberculosis.Research square · 2026Article
- Induced alanine auxotrophy as a therapeutic strategy againstbioRxiv : the preprint server for biology · 2026Article
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Emerging therapeutic drug targets in amino acid and protein biosynthesis pathways against ESKAPE and non-ESKAPE pathogens: a comprehensive review.Archives of microbiology · 2026Review
- Systems-level characterization of EGFR kinase inhibitors reveals heterogeneous effects on Mtb-macrophage interactions.bioRxiv : the preprint server for biology · 2025Article
- Article
- A pH-dependent direct sulfhydrylation pathway is required for the pathogenesis of Mycobacterium tuberculosis.Communications biology · 2025Article
- Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.Nature communications · 2024Article
- Review
- Amino Acid Biosynthesis Inhibitors in Tuberculosis Drug Discovery.Pharmaceutics · 2024Review
- bacLIFE: a user-friendly computational workflow for genome analysis and prediction of lifestyle-associated genes in bacteria.Nature communications · 2024Article
- Cyclobutanone Inhibitors of Diaminopimelate Desuccinylase (DapE) as Potential New Antibiotics.International journal of molecular sciences · 2024Article
- Large-scale Pan Genomic Analysis ofEvolutionary bioinformatics online · 2024Article
- The Bro-Xre toxin-antitoxin modules inFrontiers in microbiology · 2024Article
- Shigella Serotypes Associated With Carriage in Humans Establish Persistent Infection in Zebrafish.The Journal of infectious diseases · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
A major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication of persistent infections. Here, we uncover a vulnerable component of Mycobacterium tuberculosis (Mtb) persistence metabolism, the aspartate pathway. Rapid death of threonine and homoserine auxotrophs points to a distinct susceptibility of Mtb to inhibition of this pathway. Combinatorial metabolomic and transcriptomic analysis reveals that inability to produce threonine leads to deregulation of aspartate kinase, causing flux imbalance and lysine and DAP accumulation. Mtb's adaptive response to this metabolic stress involves a relief valve-like mechanism combining lysine export and catabolism via aminoadipate. We present evidence that inhibition of the aspartate pathway at different branch-point enzymes leads to clearance of chronic infections. Together these findings demonstrate that the aspartate pathway in Mtb relies on a combination of metabolic control mechanisms, is required for persistence, and represents a target space for anti-tuberculosis drug development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.