1. Interactions of polymyxin B with lipopolysaccharide-containing membranes.
- Author
-
Goode A, Yeh V, and Bonev BB
- Subjects
- Anti-Bacterial Agents pharmacology, Escherichia coli, Polymyxins, Lipopolysaccharides, Polymyxin B pharmacology
- Abstract
Bacterial resistance to antibiotics constantly remodels the battlefront between infections and antibiotic therapy. Polymyxin B, a cationic peptide with an anti-Gram-negative spectrum of activity is re-entering use as a last resort measure and as an adjuvant. We use fluorescence dequenching to investigate the role of the rough chemotype bacterial lipopolysaccharide from E. coli BL21 as a molecular facilitator of membrane disruption by LPS. The minimal polymyxin B/lipid ratio required for leakage onset increased from 5.9 × 10
-4 to 1.9 × 10-7 in the presence of rLPS. We confirm polymyxin B activity against E. coli BL21 by the agar diffusion method and determined a MIC of 291 μg ml-1 . Changes in lipid membrane stability and dynamics in response to polymyxin and the role of LPS are investigated by31 P NMR and high resolution31 P MAS NMR relaxation is used to monitor selective molecular interactions between polymyxin B and rLPS within bilayer lipid membranes. We observe a strong facilitating effect from rLPS on the membrane lytic properties of polymyxin B and a specific, pyrophosphate-mediated process of molecular recognition of LPS by polymyxin B.- Published
- 2021
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