ArticleMolecular biology and evolution2018
Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.
Article in Molecular biology and evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- Functional analysis of natural variation in the RNA-binding protein CsrA across the bacterial domain predicts regulatory activity.Nucleic acids research · 2026Article
- Antimicrobial Resistance and Biofilm in Bacteria from Rehabilitated Sapajus libidinosus.EcoHealth · 2026Article
- Intersecting realms of resistance: the epidemiology of Staphylococcus aureus carriage and multidrug resistance in primary healthcare settings in Recife, Brazil.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- Swarm-seq Reveals Functional Divergence in CsrA Homologs Across Bacteria.bioRxiv : the preprint server for biology · 2025Article
- Drug delivery dynamics dictate evolution of bacterial antibiotic responses.The ISME journal · 2025Article
- Feature selection and aggregation for antibiotic resistance GWAS inFrontiers in microbiology · 2025Article
- Resistance Profiling of Predominant Non-BioMed research international · 2025Article
- Dynamics of drug delivery determines course of evolution of antibiotic responses in bacteria.bioRxiv : the preprint server for biology · 2024Article
- Intraspecific variation in antibiotic resistance potential withinMicrobiology spectrum · 2024Article
- Gene expression tradeoffs determine bacterial survival and adaptation to antibiotic stress.bioRxiv : the preprint server for biology · 2024Article
- Enhance antibiotic resistance and human health risks in aerosols during the COVID-19 pandemic.The Science of the total environment · 2023Article
- Article
- Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations.Computational and structural biotechnology journal · 2022Article
- Patterns of Antibiotic Resistance inThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Article
- Gene Amplification Uncovers Large Previously Unrecognized Cryptic Antibiotic Resistance Potential in E. coli.Microbiology spectrum · 2021Article
- Can domestic pigeon be a potential carrier of zoonotic Salmonella?Transboundary and emerging diseases · 2021Article
- Spurious regulatory connections dictate the expression-fitness landscape of translation factors.Molecular systems biology · 2021Article
- A two-step PCR assembly for construction of gene variants across large mutational distances.Biology methods & protocols · 2021Article
- Extreme Antagonism Arising from Gene-Environment Interactions.Biophysical journal · 2020Article
- Azithromycin resistance mutations inMicrobial genomics · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 3 countries.
Funding
Abstract
Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses.
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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.