A research study has indicated how Gram-negative bacteria such as Escherichia coli construct their outer membrane to resemble body armour. Understanding this mechanism has important implications for the development of antibiotics.
The study was led by Professor Colin Kleanthous from the University of Oxford, and this involved microscopic examination of the outer membrane of E. coli in order to understand the molecular basis for the protection the structure affords against several classes of antibiotics.
Antimicrobial resistance is a complex concept. There are various factors to consider including the type of infecting bacterium, its location in the body, the distribution of the antibiotic in the body and its concentration at the site of infection, plus the immune status of the patient.
While most E. coli strains are harmless, the pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans.
The research considered the outer membrane, which is composed of two types of lipids and these stack on top of each other in a specific configuration. The unusual arrangement plays a role in making the membrane resistant to antibiotics.
The membrane also contains numerous proteins which the bacterium relies on to acquire nutrients and excrete waste products. Earlier research had suggested that these proteins are dotted randomly in the membrane and they do not impact upon the cell stability or structure.
However, the new research did not accept this and set out to consider if protein interactions play a role in the structural integrity of the outer membrane?
This issue was addressed through state-of-the-art experimental approaches and computer simulations. The researchers demonstrated, by tagging the outer face of proteins within the outer membrane with photoreactive chemicals, that each protein was surrounded by a ring of stacked lipids and that these lipids were shared with neighbouring membrane proteins.
The resulting network of promiscuous protein-lipid-protein complexes spans the entire bacterial surface and it is embedded within it hexagonal lattices. These lattices may well play a role in strengthening protective body armour.
This means the new research alters established thinking about the outer membrane of the bacterial cell, including its physical characteristics and how it is built. In particular, each protein appear to be connected to every other protein in the membrane by a network of lipids.
This creates a creating cellular armour plating can help to enhance resistance and developers of medicines need to account for this in future antibiotic design.
The research appears in the journal Science Advances, titled “Lipids mediate supramolecular outer membrane protein assembly in bacteria.”
