ArticleAntimicrobial agents and chemotherapy2015
Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Article
- Fluorescent Antibiotics: Bridging Diagnostic and Therapy in the Fight against Bacterial Infections.Small science · 2025Review
- Corynoxeine Supplementation Ameliorates Colistin-Induced Kidney Oxidative Stress and Inflammation in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- L-carnitine co-administration prevents colistin-induced mitochondrial permeability transition and reduces the risk of acute kidney injury in mice.Scientific reports · 2024Article
- Recent Advances in the Development of Polymyxin Antibiotics: 2010-2023.ACS infectious diseases · 2024Review
- Design, synthesis and antibacterial activity of novel colistin derivatives with thioether bond-mediated cyclic scaffold.The Journal of antibiotics · 2023Article
- Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.Antimicrobial agents and chemotherapy · 2023Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Polymyxin B-induced rhabdomyolysis: A case report.Medicine · 2020Article
- Fluorescent antibiotics for real-time tracking of pathogenic bacteria.Journal of pharmaceutical analysis · 2020Review
- Design of Next Generation Polymyxins with Lower Toxicity: The Discovery of SPR206.ACS infectious diseases · 2019Article
- Profluorescent Fluoroquinolone-Nitroxides for Investigating Antibiotic⁻Bacterial Interactions.Antibiotics (Basel, Switzerland) · 2019Article
- METTL3/mFrontiers in pharmacology · 2019Article
- Intracellular localization of polymyxins in human alveolar epithelial cells.The Journal of antimicrobial chemotherapy · 2019Article
- Polymyxin B causes DNA damage in HK-2 cells and mice.Archives of toxicology · 2018Article
- A Population WB-PBPK Model of Colistin and its Prodrug CMS in Pigs: Focus on the Renal Distribution and Excretion.Pharmaceutical research · 2018Article
- Clinical Pharmacokinetics and Pharmacodynamics of Colistin.Clinical pharmacokinetics · 2017Review
- Design and Evaluation of Novel Polymyxin Fluorescent Probes.Sensors (Basel, Switzerland) · 2017Article
- Investigating the Interaction of Octapeptin A3 with Model Bacterial Membranes.ACS infectious diseases · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Polymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity.
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Registered trials
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