Phenylene ethynylenes comprise a prototypical class of synthetic
antimicrobial compounds that mimic antimicrobial peptides produced
by eukaryotes and have broad-spectrum antimicrobial activity.
We show unambiguously that bacterial membrane permeation
by these antimicrobials depends on the presence of negative
intrinsic curvature lipids, such as phosphatidylethanolamine (PE)
lipids, found in high concentrations within bacterial membranes.
Plate-killing assays indicate that a PE-knockout mutant strain of
Escherichia coli drastically out-survives the wild type against the
membrane-active phenylene ethynylene antimicrobials, whereas
the opposite is true when challenged with traditional metabolic
antibiotics. That the PE deletion is a lethal mutation in normative
environments suggests that resistant bacterial strains do not
evolve because a lethal mutation is required to gain immunity. PE
lipids allow efficient generation of negative curvature required for
the circumferential barrel of an induced membrane pore; an inverted
hexagonal HII phase, which consists of arrays of water
channels, is induced by a small number of antimicrobial molecules.
The estimated antimicrobial occupation in these water channels is
nonlinear and jumps from
1 to 3 per 4 nmof induced water channel
length as the global antimicrobial concentration is increased. By
comparing to exactly solvable 1D spin models for magnetic systems,
we quantify the cooperativity of these antimicrobials.