ArticleThe Journal of biological chemistry2016
Molecular Basis of Filtering Carbapenems by Porins from β-Lactam-resistant Clinical Strains of Escherichia coli.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 76 citations in OpenAlex.
- Random Forest Modeling to Predict Small Molecule Accumulation in Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- Metabolic control of porin permeability influences antibiotic resistance in Escherichia coli.Nature microbiology · 2025Article
- Understanding Drug Permeability inLife (Basel, Switzerland) · 2025Review
- A unified annotation scheme for class D β-lactamases.Antimicrobial agents and chemotherapy · 2025Article
- Seeking Correlation Among Porin Permeabilities and Minimum Inhibitory Concentrations Through Machine Learning: A Promising Route to the Essential Molecular Descriptors.Molecules (Basel, Switzerland) · 2025Article
- Electrophysiological Insights into Antibiotic Translocation and Resistance: The Impact of Outer Membrane Proteins.Membranes · 2024Review
- Revealing the single-channel characteristics of OprD (OccAB1) porins from hospital strains of Acinetobacter baumannii.European biophysics journal : EBJ · 2023Article
- Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives.International journal of molecular sciences · 2023Review
- Recurrent emergence ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cefotaxime Exposure Selects Mutations within the CA-Domain ofMicrobiology spectrum · 2022Article
- An Outer Membrane Vesicle-Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability.Advanced healthcare materials · 2022Article
- Comparative Genomics Revealed Fluoroquinolone Resistance Determinants and OmpF Deletion in Carbapenem-ResistantFrontiers in microbiology · 2022Article
- Article
- An antibiotic-resistance conferring mutation in a neisserial porin: Structure, ion flux, and ampicillin binding.Biochimica et biophysica acta. Biomembranes · 2021Article
- The Influence of Permeability through Bacterial Porins in Whole-Cell Compound Accumulation.Antibiotics (Basel, Switzerland) · 2021Article
- Proteomic Charting of Imipenem Adaptive Responses in a Highly Carbapenem Resistant ClinicalAntibiotics (Basel, Switzerland) · 2021Article
- Emerging Transcriptional and Genomic Mechanisms Mediating Carbapenem and Polymyxin Resistance inmSystems · 2020Review
- Permeation of β-Lactamase Inhibitors through the General Porins of Gram-Negative Bacteria.Molecules (Basel, Switzerland) · 2020Article
- Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria.Nature reviews. Microbiology · 2020Review
- A Unified Numbering Scheme for Class C β-Lactamases.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integral membrane proteins known as porins are the major pathway by which hydrophilic antibiotics cross the outer membrane of Gram-negative bacteria. Single point mutations in porins can decrease the permeability of an antibiotic, either by reduction of channel size or modification of electrostatics in the channel, and thereby confer clinical resistance. Here, we investigate four mutant OmpC proteins from four different clinical isolates of Escherichia coli obtained sequentially from a single patient during a course of antimicrobial chemotherapy. OmpC porin from the first isolate (OmpC20) undergoes three consecutive and additive substitutions giving rise to OmpC26, OmpC28, and finally OmpC33. The permeability of two zwitterionic carbapenems, imipenem and meropenem, measured using liposome permeation assays and single channel electrophysiology differs significantly between OmpC20 and OmpC33. Molecular dynamic simulations show that the antibiotics must pass through the constriction zone of porins with a specific orientation, where the antibiotic dipole is aligned along the electric field inside the porin. We identify that changes in the vector of the electric field in the mutated porin, OmpC33, create an additional barrier by "trapping" the antibiotic in an unfavorable orientation in the constriction zone that suffers steric hindrance for the reorientation needed for its onward translocation. Identification and understanding the underlying molecular details of such a barrier to translocation will aid in the design of new antibiotics with improved permeation properties in Gram-negative bacteria.
Indexed as
Identifiers
What OpenQuestion holds
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.