Migration of 4-Hexylresorcinol Through Escherichia coli Cell Membranes

This study demonstrates the effect of phenolic lipid 4-hexylresorcinol (4HR) on gram-negative Escherichia coli K12 bacteria, leading to cytodifferentiation and affecting cell morphology and viability. It is shown that the effect of 4HR on cells is dose-dependent and develops over time. The diffusion of 4HR through the outer and inner E. coli membranes is studied by molecular dynamic methods in the full-atomic approximation. The process of 4HR transport through the lipid bilayer and the porin protein channel is studied by the methods of controlled molecular dynamics and umbrella sampling. It is shown that 4HR affects the membrane density. It freely penetrates into the bilayer located parallel to the lipid molecules at the junction of hydrophilic polar heads and hydrophobic tails. The diffusion of 4HR into the cell is more likely to occur directly through the lipid bilayer rather than the porin channel: 4HR and its clusters can bind to the L6 loop of the porin, switching the channel into the closed state.