ArticleProceedings of the National Academy of Sciences of the United States of America2022
Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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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.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Identification of chemical features for improved outer membrane permeation in mycobacteria using machine learning.Nature microbiology · 2026Article
- Direct bacterial transcript visualization illuminates spatiotemporal environmental adaptation ofScience advances · 2026Article
- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.Cell reports · 2026Article
- Impact of Diabetes Mellitus in Tuberculosis (TB) Patients on TB Transmission.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Measuring Membrane Fluidity in Live Mycobacteria Reveals Subcellular Lateral Variation And Pole-Selective Responses to Mycomembrane Perturbation.ACS infectious diseases · 2026Article
- Heteroresistance inFrontiers in cellular and infection microbiology · 2026Review
- 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
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- NProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The identification Mycobacterium tuberculosis genes that modulate long term survival in the presence of rifampicin and streptomycin.Scientific reports · 2025Article
- Structural insights into terminal arabinosylation of mycobacterial cell wall arabinan.Nature communications · 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
- Identification of chemical features that influence mycomembrane permeation and antitubercular activity.bioRxiv : the preprint server for biology · 2025Article
- Building Spatiotemporal Understanding ofACS infectious diseases · 2025Review
- Identification of Axinellamines A and B as Anti-Tubercular Agents.Marine drugs · 2024Article
- Propionate prevents loss of the PDIM virulence lipid in Mycobacterium tuberculosis.Nature microbiology · 2024Article
- Transposon sequencing reveals metabolic pathways essential for Mycobacterium tuberculosis infection.PLoS pathogens · 2024Article
- The PDIM paradox ofbioRxiv : the preprint server for biology · 2023Article
- Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.Trends in immunology · 2023Review
- Mycobacterium tuberculosis Requires the Outer Membrane Lipid Phthiocerol Dimycocerosate for Starvation-Induced Antibiotic Tolerance.mSystems · 2023Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 1 country.
Funding
Abstract
Current chemotherapy against Mycobacterium tuberculosis (Mtb), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug–drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, host environments profoundly affect the bacterial metabolic state and drug efficacy, limiting the accuracy of predictions based on in vitro assays alone. In this study, we utilized conditional Mtb knockdown mutants of essential genes as an experimentally tractable surrogate for drug treatment and probe the relationship between Mtb carbon metabolism and chemical–genetic interactions (CGIs). We examined the antitubercular drugs isoniazid, rifampicin, and moxifloxacin and found that CGIs are differentially responsive to the metabolic state, defining both environment-independent and -dependent interactions. Specifically, growth on the in vivo–relevant carbon source, cholesterol, reduced rifampicin efficacy by altering mycobacterial cell surface lipid composition. We report that a variety of perturbations in cell wall synthesis pathways restore rifampicin efficacy during growth on cholesterol, and that both environment-independent and cholesterol-dependent in vitro CGIs could be leveraged to enhance bacterial clearance in the mouse infection model. Our findings present an atlas of chemical–genetic–environmental interactions that can be used to optimize drug–drug interactions, as well as provide a framework for understanding in vitro correlates of in vivo efficacy.
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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.