Effect of sodium deoxycholate sulfate on outer membrane permeability and neutralization of bacterial...

Area of Science:

• Antimicrobial drug development
• Bacterial membrane interactions
• Lipopolysaccharide (LPS) complexation

Background:

• Polymyxin B (PMB) is a critical antibiotic for treating infections caused by Gram-negative bacteria.
• Lipopolysaccharides (LPS) are key components of the outer membrane of Gram-negative bacteria and are targets for PMB.
• Understanding the interaction between PMB formulations and LPS is crucial for optimizing antibiotic efficacy.

Purpose of the Study:

• To investigate the binding interactions of different polymyxin B (PMB) formulations with lipopolysaccharides (LPS).
• To evaluate the structural stability, particle size, and bacterial uptake of PMB-LPS complexes.
• To determine the efficacy of PMB formulations against Gram-negative bacteria like Escherichia coli and Pseudomonas aeruginosa.

Main Methods:

• Binding assays to quantify the interaction between PMB, PMB:sodium deoxycholate sulfate (SDCS) formulations (1:2 and 1:3 ratios), and a commercial PMB formulation (CPMB) with LPS.
• Particle size analysis of PMB-LPS complexes.
• Molecular docking simulations to predict the structure and stability of PMB-LPS complexes.
• Bacterial uptake studies and antimicrobial efficacy testing against E. coli and P. aeruginosa.

Main Results:

• The 1:2 PMB:SDCS formulation exhibited distinct binding characteristics and smaller particle sizes in the presence of LPS compared to other formulations.
• Molecular docking revealed that the 1:2 PMB formulation formed a more stable PMB-LPS complex, primarily stabilized by hydrogen bonds and salt bridges.
• The 1:2 PMB formulation demonstrated higher bacterial uptake and effective neutralization of LPS micelles, leading to antimicrobial activity against E. coli and P. aeruginosa.

Conclusions:

• The 1:2 PMB:SDCS formulation shows superior binding affinity, stability, and bacterial uptake compared to other tested PMB formulations.
• This formulation effectively disrupts LPS membranes and exhibits potent antimicrobial activity against key Gram-negative pathogens.
• The findings suggest that optimizing PMB formulations can enhance their therapeutic potential against LPS-expressing bacteria.