ArticlePloS one2011
Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 137 citations in OpenAlex.
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- Medicinal Plants: A Promising Therapeutic Approach for Addressing Antimicrobial Resistance.International journal of molecular sciences · 2026Review
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- Navigating the copper highway: bacterial strategies for cytoplasmic import.Journal of inorganic biochemistry · 2026Review
- Augmentation of antibacterial activity of ciprofloxacin by bisabololoxide A encapsulated in polymeric nanoparticles against uropathogenic Escherichia coli.BMC biotechnology · 2025Article
- Evolution of beta-lactam resistance causes fitness reductions and several cases of collateral sensitivities in the human pathogenAntimicrobial agents and chemotherapy · 2025Article
- Understanding Drug Permeability inLife (Basel, Switzerland) · 2025Review
- Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria.RSC chemical biology · 2025Article
- An Overview of the Epidemiology of Multidrug Resistance and Bacterial Resistance Mechanisms: What Solutions Are Available? A Comprehensive Review.Microorganisms · 2025Review
- Sequence variability of BamA and FadL candidate vaccinogens suggests divergent evolutionary paths ofJournal of bacteriology · 2025Article
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- Antimicrobial resistance in orthopedics: microbial insights, clinical impact, and the necessity of a multidisciplinary approach-a review.Acta orthopaedica · 2025Review
- Mechanisms ofMicroorganisms · 2025Article
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- The Role of the Hfq Protein in Bacterial Resistance to Antibiotics: A Narrative Review.Microorganisms · 2025Review
- Interplay between porin deficiency, fitness, and virulence in carbapenem-non-susceptible Pseudomonas aeruginosa and Enterobacteriaceae.PLoS pathogens · 2025Review
- High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations.Nature communications · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Antibiotic-resistant bacteria, particularly gram negative species, present significant health care challenges. The permeation of antibiotics through the outer membrane is largely effected by the porin superfamily, changes in which contribute to antibiotic resistance. A series of antibiotic resistant E. coli isolates were obtained from a patient during serial treatment with various antibiotics. The sequence of OmpC changed at three positions during treatment giving rise to a total of four OmpC variants (denoted OmpC20, OmpC26, OmpC28 and OmpC33, in which OmpC20 was derived from the first clinical isolate). We demonstrate that expression of the OmpC K12 porin in the clinical isolates lowers the MIC, consistent with modified porin function contributing to drug resistance. By a range of assays we have established that the three mutations that occur between OmpC20 and OmpC33 modify transport of both small molecules and antibiotics across the outer membrane. This results in the modulation of resistance to antibiotics, particularly cefotaxime. Small ion unitary conductance measurements of the isolated porins do not show significant differences between isolates. Thus, resistance does not appear to arise from major changes in pore size. Crystal structures of all four OmpC clinical mutants and molecular dynamics simulations also show that the pore size is essentially unchanged. Molecular dynamics simulations suggest that perturbation of the transverse electrostatic field at the constriction zone reduces cefotaxime passage through the pore, consistent with laboratory and clinical data. This subtle modification of the transverse electric field is a very different source of resistance than occlusion of the pore or wholesale destruction of the transverse field and points to a new mechanism by which porins may modulate antibiotic passage through the outer membrane.
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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.