Physics

Viscosity

Bacterial outer membrane

Biotechnology

Organic chemistry

In vivo

Polymyxin

Membrane

Antibiotics

Bacteria

Escherichia coli

Biology

Microbiology

Gene

Biophysics

Chemistry

Immunology

Polymyxin B

Lipopolysaccharide

Phase (matter)

Genetics

Biochemistry

Thermodynamics

Proceedings of the National Academy of Sciences

Significance Gram-negative bacteria possess an outer membrane (OM) which reduces antibiotic effectiveness. The OM has a dense outer layer of lipopolysaccharide (LPS), a glycolipid which is directly targeted by the last-resort antibiotic polymyxin B (PmB). However, we lack accurate molecular data on the PmB–OM interaction to inform future drug development. Here we study the PmB–OM interaction in vitro and show that in vivo results are reproduced only when the LPS is in a liquid crystalline phase, which occurs at body temperature. These findings not only explain the temperature dependence of PmB function but also support the notion that bacteria actively control the viscosity of their outer membranes as growth temperatures vary.

Liquid crystalline bacterial outer membranes are critical for antibiotic susceptibility