ArticleNature microbiology2021
Analysing the fitness cost of antibiotic resistance to identify targets for combination antimicrobials.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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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Who cites it
32 citing papers in PubMed.
- Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.Molecular biology reports · 2026Review
- Mutations in RNA polymerase that drive the emergence of antibiotic resistance.Current opinion in microbiology · 2026Review
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Association of Staphylococcus aureus bloodstream infection with 7-day incident delirium in critically Ill adults: a propensity-weighted competing risk analysis.BMC infectious diseases · 2026Article
- Genome scale CRISPRi reveals both shared and strain-specific vulnerabilities in genetically diverse drug-resistant strains of Mycobacterium tuberculosis.Nature communications · 2026Article
- Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.Nature microbiology · 2026Article
- ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.bioRxiv : the preprint server for biology · 2026Article
- The genetic landscape of antibiotic sensitivity inScience advances · 2026Article
- Mitochondrial heterogeneity drives the evolution of fungicide resistance inScience advances · 2026Article
- Transcription co-inhibition alters drug resistance evolution and enhances Mycobacterium tuberculosis clearance from granulomas.Nature microbiology · 2026Article
- MazF endoribonuclease promotes resolution of transcription-replication conflicts at ribosomal RNA genes in Escherichia coli.Nucleic acids research · 2025Article
- One Earth-One Health to Combat Antimicrobial Resistance Having a Dual Mutation Pattern, Based on the Robust Self-Regulation and Perpetual Reconstruction of Ecosystems.Antibiotics (Basel, Switzerland) · 2025Article
- Coevolutionary history of predation constrains the evolvability of antibiotic resistance in prey bacteria.npj antimicrobials and resistance · 2025Article
- Phenotypic and genetic stepwise changes inAntimicrobial agents and chemotherapy · 2025Article
- Large-scale combination screens reveal small-molecule sensitization of antibiotic-resistant gram-negative ESKAPE pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- In the shadow of antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Broad-spectrum tolerance to disinfectant-mediated bacterial killing due to mutation of the PheS aminoacyl tRNA synthetase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A universal and wide-range cytosine base editor via domain-inlaid and fidelity-optimized CRISPR-FrCas9.Nature communications · 2025Article
- Gut Distribution, Impact Factor, and Action Mechanism of Bacteriocin-Producing Beneficial Microbes as Promising Antimicrobial Agents in Gastrointestinal Infection.Probiotics and antimicrobial proteins · 2024Review
- Shaping of microbial phenotypes by trade-offs.Nature communications · 2024Review
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16 authors.
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Abstract
Mutations in the rifampicin (Rif)-binding site of RNA polymerase (RNAP) confer antibiotic resistance and often have global effects on transcription that compromise fitness and stress tolerance of resistant mutants. We suggested that the non-essential genome, through its impact on the bacterial transcription cycle, may represent an untapped source of targets for combination antimicrobial therapies. Using transposon sequencing, we carried out a genome-wide analysis of fitness cost in a clinically common rpoB H526Y mutant. We find that genes whose products enable increased transcription elongation rates compound the fitness costs of resistance whereas genes whose products function in cell wall synthesis and division mitigate it. We validate our findings by showing that the cell wall synthesis and division defects of rpoB H526Y result from an increased transcription elongation rate that is further exacerbated by the activity of the uracil salvage pathway and unresponsiveness of the mutant RNAP to the alarmone ppGpp. We applied our findings to identify drugs that inhibit more readily rpoB H526Y and other Rif
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