A new study published in the journal Science Advances sheds light on how Gram-negative bacteria like E. coli construct their outer membrane to resemble body armour, which has far-reaching implications for the development of antibiotics.

They undertook a microscopic examination of the outer membrane of E. coli to understand the molecular basis for the protection it affords against many classes of antibiotics. E. coli causes infections such as pneumonia, UTIs and sepsis that are notoriously difficult to treat due to multidrug resistance.

The outer membrane is composed of two types of lipids that stack on top of each other, an unusual arrangement, responsible for making the membrane resistant to antibiotics. the outer membrane contains numerous proteins which the bacterium relies on to acquire nutrients and excrete waste products.

By tagging the outer face of proteins within the outer membrane with photoreactive chemicals, they found that not only was each protein surrounded by a ring of stacked lipids but that these lipids were shared with neighbouring membrane proteins.

Even more surprising was the finding that the resulting network of promiscuous protein-lipid-protein complexes spans the entire bacterial surface and embedded within it hexagonal lattices reminiscent of those used to strengthen protective body armour.

Professor Kleanthous explains. ‘Every protein appears connected to every other protein in the membrane by a network of lipids, creating cellular armour plating that researchers will need to take account of in future antibiotic design.’