ReviewNature protocols2021
An LC-MS/MS assay and complementary web-based tool to quantify and predict compound accumulation in E. coli.
Review in Nature protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Random Forest Modeling to Predict Small Molecule Accumulation in Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- Aerocavin Is an Antibiotic with Potent and Specific Anti-Neisserial Activity.ACS infectious diseases · 2026Article
- Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.Journal of medicinal chemistry · 2026Article
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Click-based determination of accumulation of molecules in Escherichia coli.Nature communications · 2026Article
- The Quantification of Drug Accumulation within Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- RND efflux pump inhibitor-like natural products as antibiotic adjuvants against multidrug-resistant gram-negative bacteria: a graded-evidence review.Frontiers in microbiology · 2026Review
- Light-Activated Metal-Dependent Protein Degradation: A Heterobifunctional Ruthenium(II) Photosensitizer Targeting New Delhi Metallo-β-lactamase 1.Journal of the American Chemical Society · 2025Article
- Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria.ACS infectious diseases · 2025Article
- Measurement and prediction of small molecule retention by Gram-negative bacteria based on a large-scale LC/MS screen.Scientific reports · 2025Article
- New Generation Modified Azole Antifungals against Multidrug-ResistantJournal of medicinal chemistry · 2025Article
- Rational search for natural antimicrobial compounds: relevance of sesquiterpene lactones.Natural products and bioprospecting · 2025Article
- Article
- Discovery of a Pseudomonas aeruginosa-specific small molecule targeting outer membrane protein OprH-LPS interaction by a multiplexed screen.Cell chemical biology · 2025Article
- Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens.Nature microbiology · 2025Article
- New Insights into the Mechanism of Action of L-681,217, a Medicinally Promising Polyketide Inhibitor of Bacterial Protein Translation.Biochemistry · 2024Article
- Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane.Communications biology · 2024Article
- Mass Spectrometry Quantification of Anticancer Drug Uptake in Single Multicellular Tumor Spheroids.ACS pharmacology & translational science · 2024Article
- Bioluminescence-Based Determination of Cytosolic Accumulation of Antibiotics inACS infectious diseases · 2024Article
- Using permeation guidelines to design new antibiotics-A PASsagE into Pseudomonas aeruginosa.Clinical and translational medicine · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Novel classes of broad-spectrum antibiotics have been extremely difficult to discover, largely due to the impermeability of the Gram-negative membranes coupled with a poor understanding of the physicochemical properties a compound should possess to promote its accumulation inside the cell. To address this challenge, numerous methodologies for assessing intracellular compound accumulation in Gram-negative bacteria have been established, including classic radiometric and fluorescence-based methods. The recent development of accumulation assays that utilize liquid chromatography-tandem mass spectrometry (LC-MS/MS) have circumvented the requirement for labeled compounds, enabling assessment of a substantially broader range of small molecules. Our unbiased study of accumulation trends in Escherichia coli using an LC-MS/MS-based assay led to the development of the eNTRy rules, which stipulate that a compound is most likely to accumulate in E. coli if it has an ionizable Nitrogen, has low Three-dimensionality and is relatively Rigid. To aid in the implementation of the eNTRy rules, we developed a complementary web tool, eNTRyway, which calculates relevant properties and predicts compound accumulation. Here we provide a comprehensive protocol for analysis and prediction of intracellular accumulation of small molecules in E. coli using an LC-MS/MS-based assay (which takes ~2 d) and eNTRyway, a workflow that is readily adoptable by any microbiology, biochemistry or chemical biology laboratory.
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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.