Biophysical studies of interaction of potential antibiotics with model cellular membrane

Abstract

The inability of current antibiotics to act against multidrug-resistant pathogens requires the discovery of novel molecules. One of the pathways through which these molecules can hinder bacterial cell functionality is to alter the membrane morphology. The current thesis explores the effects of various potential antibiotics on these membranes which have been modelled using lipids of different charges and hydrophobicity. Ionic liquids, the most prominent future antibiotics, are found to induce an interdigitated phase in the membrane forming a thinner bilayer that could alter the permeability of the membrane. Another prospective molecule, the violacein, is observed to interact with membranes predominantly depending on the hydrophobicity of the lipids. The plant protein, Kalata B1 indicates a stable complex formation with an anionic lipid. All these interactions have been quantified thermodynamically using the Langmuir-Blodgett technique and differential scanning calorimetry. The detailed structural characterizations have been done by advanced X-ray scattering techniques. Therefore, the thesis presents comprehensive biophysical studies on the membrane perturbation capability of potential antibiotics which could help in developing new drug molecules in near future.