ArticleProceedings of the National Academy of Sciences of the United States of America2011
Depletion of antibiotic targets has widely varying effects on growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed.
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Modular toolkit to facilitate molecular manipulations in mycobacteria.Journal of bacteriology · 2026Article
- Uncovering Insights Into the Biology of Mycobacterium tuberculosis Using Genetic Tools.MicrobiologyOpen · 2025Review
- Targeted protein degradation in Escherichia coli using CLIPPERs.EMBO reports · 2025Article
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy.Nature communications · 2024Article
- Genetic manipulation of giant viruses and their host, Acanthamoeba castellanii.Nature protocols · 2024Review
- The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions.The Journal of clinical investigation · 2023Review
- TheMicroorganisms · 2023Article
- Identification of anti-Acta pharmaceutica Sinica. B · 2023Article
- Antibacterial and anti-biofilm activity of plumbagin against multi-drug resistant clinical bacterial isolates.Saudi medical journal · 2022Article
- Evaluation of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase (DAHPS) as a Vulnerable Target in Mycobacterium tuberculosis.Microbiology spectrum · 2022Article
- Bacterial degrons in synthetic circuits.Open biology · 2022Review
- Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling.Cell chemical biology · 2022Article
- Gradients in gene essentiality reshape antibacterial research.FEMS microbiology reviews · 2022Review
- Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- EPSP Synthase-Depleted Cells Are Aromatic Amino Acid Auxotrophs in Mycobacterium smegmatis.Microbiology spectrum · 2021Article
- Impact of Target Turnover on the Translation of Drug-Target Residence Time to Time-Dependent Antibacterial Activity.ACS infectious diseases · 2021Article
- Article
- Redox homeostasis in Mycobacterium tuberculosis is modulated by a novel actinomycete-specific transcription factor.The EMBO journal · 2021Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
It is often assumed that antibiotics act on the most vulnerable cellular targets, particularly those that require limited inhibition to block growth. To evaluate this assumption, we developed a genetic method that can inducibly deplete targeted proteins and that mimics their chemical inactivation. We applied this system to current antibiotic targets in mycobacteria. Although depleting some antibiotic targets significantly perturbs bacterial growth, surprisingly, we found that reducing the levels of other targets by more than 97% had little or no effect on growth. For one of these targets, dihydrofolate reductase, metabolic analysis suggested that depletion mimics the use of subinhibitory concentrations of the antibiotic trimethroprim. These observations indicate that some drug targets can exist at levels much higher than are needed to support growth. However, protein depletion can be used to identify promising drug targets that are particularly vulnerable to inhibition.
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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.