ArticleThe Journal of antimicrobial chemotherapy2020
A novel colistin adjuvant identified by virtual screening for ArnT inhibitors.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Repurposing flufenamic acid as a putative PmrB-directed adjuvant to restore colistin activity inMicrobiology spectrum · 2026Article
- Exploration of the aromatic abietane diterpenoid scaffold in the development of ArnT-mediated colistin resistance inhibitors.RSC advances · 2026Article
- Natural compounds: a promising therapeutic option for managing colistin-resistant bacteria and improving colistin activity.Molecular biology reports · 2026Review
- PFK-158 enhances colistin efficacy against resistantFrontiers in veterinary science · 2026Article
- Biological Evaluation and Computational Modelling Studies onCurrent pharmaceutical design · 2025Article
- Untying the anchor for the lipopolysaccharide: lipid A structural modification systems offer diagnostic and therapeutic options to tackle polymyxin resistance.Arhiv za higijenu rada i toksikologiju · 2023Review
- Regulatory Landscape of theAntibiotics (Basel, Switzerland) · 2023Article
- A comprehensive review on genomics, systems biology and structural biology approaches for combating antimicrobial resistance in ESKAPE pathogens: computational tools and recent advancements.World journal of microbiology & biotechnology · 2022Review
- Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants.ACS infectious diseases · 2021Article
- Identification of Effective Anticancer G-Quadruplex-Targeting Chemotypes through the Exploration of a High Diversity Library of Natural Compounds.Pharmaceutics · 2021Article
- Review
- Antibiotic Adjuvant Activity Revealed in a Photoaffinity Approach to Determine the Molecular Target of Antipyocyanin Compounds.ACS infectious diseases · 2021Article
- A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-ResistantPharmaceutics · 2021Article
- Exogenous and Endogenous Phosphoethanolamine Transferases Differently Affect Colistin Resistance and Fitness inFrontiers in microbiology · 2021Article
- Article
- Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections.Molecules (Basel, Switzerland) · 2020Review
- The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections.Antibiotics (Basel, Switzerland) · 2020Review
- Biofilm Production by Carbapenem-ResistantFrontiers in cellular and infection microbiology · 2020Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColistin is a last-resort treatment option for many MDR Gram-negative bacteria. The covalent addition of l-aminoarabinose to the lipid A moiety of LPS is the main colistin resistance mechanism in the human pathogen Pseudomonas aeruginosa.
objectivesIdentification (by in silico screening of a chemical library) of potential inhibitors of ArnT, which catalyses the last committed step of lipid A aminoarabinosylation, and their validation in vitro as colistin adjuvants.
methodsThe available ArnT crystal structure was used for a docking-based virtual screening of an in-house library of natural products. The resulting putative ArnT inhibitors were tested in growth inhibition assays using a reference colistin-resistant P. aeruginosa strain. The most promising compound was further characterized for its range of activity, specificity and cytotoxicity. Additionally, the effect of the compound on lipid A aminoarabinosylation was verified by MS analyses of lipid A.
resultsA putative ArnT inhibitor (BBN149) was discovered by molecular docking and demonstrated to specifically potentiate colistin activity in colistin-resistant P. aeruginosa isolates, without relevant effect on colistin-susceptible strains. BBN149 also showed adjuvant activity against colistin-resistant Klebsiella pneumoniae and low toxicity to bronchial epithelial cells. Lipid A aminoarabinosylation was reduced in BBN149-treated cells, although only partially.
conclusionsThis study demonstrates that in silico screening targeting ArnT can successfully identify inhibitors of colistin resistance and provides a promising lead compound for the development of colistin adjuvants for the treatment of MDR bacterial infections.
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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.