ArticleMolecular systems biology2022
Growth-mediated negative feedback shapes quantitative antibiotic response.
Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Enzyme kinetics shapes the growth response of metabolic networks.PLoS computational biology · 2026Article
- Principles of bacteriostatic and bactericidal antibiotics at subinhibitory concentrations.mBio · 2025Article
- Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Ecology-based approach to predict no-effect antibiotic concentrations for minimizing environmental selection of resistance.The ISME journal · 2025Article
- How total mRNA influences cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A low-footprint, fluorescence-based bacterial time-kill assay for estimating dose-dependent cell death dynamics.bioRxiv : the preprint server for biology · 2024Article
- Diverse mutant selection windows shape spatial heterogeneity in evolving populations.PLoS computational biology · 2024Article
- Effect ofFrontiers in microbiology · 2024Article
- Diverse mutant selection windows shape spatial heterogeneity in evolving populations.bioRxiv : the preprint server for biology · 2023Article
- Dissociation kinetics of small-molecule inhibitors in Escherichia coli is coupled to physiological state of cells.Communications biology · 2023Article
- Growth-mediated negative feedback shapes quantitative antibiotic response.Molecular systems biology · 2022Article
- Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dose-response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose-response curves. The shape of the dose-response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose-response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose-response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose-response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.
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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.