ArticlemBio2020
Mechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative Infections.
Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Colistin-stabilized antisolvent precipitation enables engineering of microcrystalline niclosamide for inhalable composite powders.International journal of pharmaceutics · 2026Article
- Enzymatic Glucosylation Enhances the Solubility of Niclosamide but Abrogates Its Therapeutic Efficacy.ACS omega · 2026Article
- Colistin and Oxyclozanide co-loaded PLGA nano-microspheres to reverse colistin resistance can effectively treat colistin-resistantInternational journal of pharmaceutics: X · 2025Article
- Physiologically informed in vitro framework reveals context-dependent combinatory activity of niclosamide-colistin against Gram-negative bacteria.The Journal of antimicrobial chemotherapy · 2025Article
- New Frontiers for Old Medications: Repurposing Approved Drugs Against Gram-Negative Bacterial Infections.Microorganisms · 2025Review
- Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections.Communications biology · 2025Article
- Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides.ADMET & DMPK · 2025Article
- The Antifungal Potential of Niclosamide and Structurally Related Salicylanilides.International journal of molecular sciences · 2024Review
- Exploring Structure-Activity Relationships of Niclosamide-Based Colistin Potentiators in Colistin-Resistant Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2024Article
- Synergistic antibacterial effects of closantel and its enantiomers in combination with colistin against multidrug resistant gram-negative bacteria.Frontiers in microbiology · 2024Article
- Drug Repurposing: Research Progress of Niclosamide and Its Derivatives on Antibacterial Activity.Infection and drug resistance · 2024Review
- Colistin-niclosamide-loaded nanoemulsions and nanoemulsion gels for effective therapy of colistin-resistantFrontiers in veterinary science · 2024Article
- A metagenomic library cloning strategy that promotes high-level expression of captured genes to enable efficient functional screening.Cell chemical biology · 2023Article
- Cationic Polymers Enable Internalization of Negatively Charged Chemical Probes into Bacteria.ACS chemical biology · 2023Article
- Consistency across multi-omics layers in a drug-perturbed gut microbial community.Molecular systems biology · 2023Article
- Exogenous glutathione reverses meropenem resistance in carbapenem-resistantFrontiers in pharmacology · 2023Article
- Activating alternative transport modes in a multidrug resistance efflux pump to confer chemical susceptibility.Nature communications · 2022Article
- Drug synergy discovery of tavaborole and aminoglycosides against Escherichia coli using high throughput screening.AMB Express · 2022Article
- Study of Biological Activities and ADMET-Related Properties of Salicylanilide-Based Peptidomimetics.International journal of molecular sciences · 2022Article
- A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
One avenue to combat multidrug-resistant Gram-negative bacteria is the coadministration of multiple drugs (combination therapy), which can be particularly promising if drugs synergize. The identification of synergistic drug combinations, however, is challenging. Detailed understanding of antibiotic mechanisms can address this issue by facilitating the rational design of improved combination therapies. Here, using diverse biochemical and genetic assays, we examine the molecular mechanisms of niclosamide, a clinically approved salicylanilide compound, and demonstrate its potential for Gram-negative combination therapies. We discovered that Gram-negative bacteria possess two innate resistance mechanisms that reduce their niclosamide susceptibility: a primary mechanism mediated by multidrug efflux pumps and a secondary mechanism of nitroreduction. When efflux was compromised, niclosamide became a potent antibiotic, dissipating the proton motive force (PMF), increasing oxidative stress, and reducing ATP production to cause cell death. These insights guided the identification of diverse compounds that synergized with salicylanilides when coadministered (efflux inhibitors, membrane permeabilizers, and antibiotics that are expelled by PMF-dependent efflux), thus suggesting that salicylanilide compounds may have broad utility in combination therapies. We validate these findings
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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.