ArticleProceedings of the National Academy of Sciences of the United States of America2014
Contribution of phenotypic heterogeneity to adaptive antibiotic resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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116 citing papers in PubMed, 246 citations in OpenAlex.
- Double agent: how Escherichia coli switches from commensal to pathogen in the urinary tract infection.Infection · 2026Review
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Quantifying and Minimizing the Variance of Gradient Insulator-Based Dielectrophoresis.Micromachines · 2026Article
- AcrAB-NodT overexpression drives envelope destabilization and metal sensitivity in Caulobacter vibrioides.Archives of microbiology · 2026Review
- High-resolution, high-throughput detection of hidden antibiotic resistance with the dilution-and-delay (DnD) susceptibility assay.Nature communications · 2026Article
- Structured Promoter Variability in Epigenetically Regulated Operons Contributes to Surface Adaptation in Salmonella.Microbial biotechnology · 2026Article
- Stress-driven emergence of heritable non-genetic drug resistance.Research square · 2025Article
- Metabolic reprogramming enhances the susceptibility of multidrug- and carbapenem-resistant bacteria to antibiotics.Nature microbiology · 2025Article
- Ecological consequences of antimicrobial residues and bioactive chemicals on antimicrobial resistance in agroecosystems.Journal of advanced research · 2025Review
- Implications of gene expression heterogeneity in the interplay between acquired resistance and bacterial metabolism.Scientific reports · 2025Article
- Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis.Nature communications · 2025Article
- Stochastic gene expression in proliferating cells: Differing noise intensity in single-cell and population perspectives.PLoS computational biology · 2025Article
- Lineage-dependent variations in single-cell antibiotic susceptibility reveal the selective inheritance of phenotypic resistance in bacteria.Nature communications · 2025Article
- Ribosome phenotypes for rapid classification of antibiotic-susceptible and resistant strains of Escherichia coli.Communications biology · 2025Article
- Adaptive Resistance ofMicroorganisms · 2025Article
- Single-cell transcriptomes reveal spatiotemporal heat stress response in maize roots.Nature communications · 2025Article
- Drug delivery dynamics dictate evolution of bacterial antibiotic responses.The ISME journal · 2025Article
- Aminoglycoside heteroresistance inmBio · 2024Article
- Dynamics of drug delivery determines course of evolution of antibiotic responses in bacteria.bioRxiv : the preprint server for biology · 2024Article
- Clinically relevant mutations in regulatory regions of metabolic genes facilitate early adaptation to ciprofloxacin in Escherichia coli.Nucleic acids research · 2024Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibiotic-resistant isolates of Salmonella enterica were selected on plates containing lethal concentrations of rifampicin, kanamycin, and nalidixic acid. The stability of the resistance phenotype was scored after nonselective growth. Rifampicin-resistant (Rif(r)) isolates were stable, suggesting that they had arisen by mutation. Mutations in the rpoB gene were detected indeed in Rif(r) mutants. In contrast, a fraction of kanamycin-resistant (Km(r)) and nalidixic acid-resistant (Nal(r)) isolates showed reduced resistance after nonselective growth, suggesting that mechanisms other than mutation had contributed to bacterial survival upon lethal selection. Single-cell analysis revealed heterogeneity in expression of the porin gene ompC, and subpopulation separation provided evidence that reduced ompC expression confers adaptive resistance to kanamycin. In the case of Nal(r) isolates, mutations in the gyrA gene were present in most nalidixic acid-resistant isolates. However, the efflux pump inhibitor Phe-Arg-β-naphtylamide (PAβN) reduced the level of resistance in Nal(r) mutants, indicating that active efflux contributes to the overall level of nalidixic acid resistance. Heterogeneous efflux pump activity was detected in single cells and colonies, and a correlation between high efflux and increased resistance to nalidixic acid was found. These observations suggest that fluctuations in the expression and the activity of critical functions of the bacterial cell, alone or combined with mutations, can contribute to adaptive resistance to antibiotics.
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