ArticleNature communications2010
A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy.
Article in Nature communications, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 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
184 citing papers in PubMed, 304 citations in OpenAlex.
- An adenylyl cyclase switch reroutes carbon from growth to virulence lipids inbioRxiv : the preprint server for biology · 2026Article
- Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.Nature communications · 2026Article
- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.Cell reports · 2026Article
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Mycobacterium tuberculosis long-chain fatty acid resistome reveals universal stress protein TB15.3 as essential for infection.Communications biology · 2026Article
- ThemBio · 2026Article
- A bactericidal tuberculosis drug regimen driven by inhibition of the terminal oxidases by pretomanid.EMBO molecular medicine · 2026Article
- Structure, Mutation, Functional Domain Roles and Medical Implications of Glycerol Kinase.The protein journal · 2026Review
- Article
- Essential redundancies fuel Mycobacterium tuberculosis adaptation to the host.PLoS pathogens · 2025Review
- Mycobacterium tuberculosis overcomes phosphate starvation by extensively remodelling its lipidome with phosphorus-free lipids.Nature communications · 2025Article
- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.bioRxiv : the preprint server for biology · 2025Article
- Isoleucyl-tRNA synthetase depletion reveals vulnerabilities in Mycobacterium abscessus and Mycobacterium marinum.Communications biology · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- Article
- Knockout of glycerol metabolic pathways enables efficient mycolicibacterial phytosterol conversion using glycerol as cosovlent.Applied microbiology and biotechnology · 2025Article
- A potent phenylalkylamine disrupts mycobacterial membrane bioenergetics and augments bactericidal activity of bedaquiline.iScience · 2025Article
- Methylglyoxal is an antibacterial effector produced by macrophages during infection.Cell host & microbe · 2025Article
- Disruption of riboflavin biosynthesis in mycobacteria establishes riboflavin pathway intermediates as key precursors of MAIT cell agonists.PLoS pathogens · 2025Article
- Defining the mechanism of action of the nitrofuranyl piperazine HC2210 against Mycobacterium abscessus.npj antimicrobials and resistance · 2025Article
124 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
41 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Candidate antibacterials are usually identified on the basis of their in vitro activity. However, the apparent inhibitory activity of new leads can be misleading because most culture media do not reproduce an environment relevant to infection in vivo. In this study, while screening for novel anti-tuberculars, we uncovered how carbon metabolism can affect antimicrobial activity. Novel pyrimidine-imidazoles (PIs) were identified in a whole-cell screen against Mycobacterium tuberculosis. Lead optimization generated in vitro potent derivatives with desirable pharmacokinetic properties, yet without in vivo efficacy. Mechanism of action studies linked the PI activity to glycerol metabolism, which is not relevant for M. tuberculosis during infection. PIs induced self-poisoning of M. tuberculosis by promoting the accumulation of glycerol phosphate and rapid ATP depletion. This study underlines the importance of understanding central bacterial metabolism in vivo and of developing predictive in vitro culture conditions as a prerequisite for the rational discovery of new antibiotics.
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.