ArticleBiophysical journal2017
Membrane Cholesterol Reduces Polymyxin B Nephrotoxicity in Renal Membrane Analogs.
Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Perspective on the Application of Erythrocyte Liposome-Based Drug Delivery for Infectious Diseases.Membranes · 2022Review
- Synergistic Membrane Disturbance Improves the Antibacterial Performance of Polymyxin B.Polymers · 2022Article
- Cholesterol Stiffening of Lipid Membranes.The Journal of membrane biology · 2022Review
- Molecular Dynamics for Antimicrobial Peptide Discovery.Infection and immunity · 2021Review
- Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging.Frontiers in pharmacology · 2021Article
- How cholesterol stiffens unsaturated lipid membranes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structure-Interaction Relationship of Polymyxins with the Membrane of Human Kidney Proximal Tubular Cells.ACS infectious diseases · 2020Article
- Polymyxin Delivery Systems: Recent Advances and Challenges.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Benchtop-fabricated lipid-based electrochemical sensing platform for the detection of membrane disrupting agents.Scientific reports · 2020Article
- How do bacterial membranes resist polymyxin antibiotics?Communications biology · 2020Review
- Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions.Biophysical journal · 2019Article
- Membrane charge and lipid packing determine polymyxin-induced membrane damage.Communications biology · 2019Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state. In cholesterol depleted membranes, PmB forms clusters on the membranes leading to an indentation of the bilayers and increase in water permeation. The inserted peptides formed aggregates in the membrane core leading to further structural instabilities and increased water intake. The presence of cholesterol in the resistant membrane analogs led to a significant decrease in membrane damage. Although cholesterol did not inhibit peptide insertion, it minimized peptide clustering and water intake through stabilization of the bilayer structure and suppression of lipid and peptide mobility.
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