New study on armour-plated bacterial protection to inform future antibiotic design by Hoogenboom lab

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

The study was led by Professor Colin Kleanthous in the Department of Biochemistry at the University of Oxford, with further contributions from colleagues in Oxford. Together the scientists undertook a microscopic examination of the outer membrane of E. coli to understand the molecular basis for the protection that it provides against many classes of antibiotics.

E. coli causes infections such as pneumonia, urinary track infections and sepsis that are notoriously difficult to treat due to multidrug resistance.

Dr Georgina Benn and Professor Bart Hoogenboom at the UCL London Centre for Nanotechnology contributed to this work by providing high-resolution microscopy data, resolving how different proteins in the outer membrane are positioned with respect to each other. 

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

Textbooks classically show these proteins dotted randomly in the membrane, contributing little to its stability or structure.

By tagging the outside of proteins within the outer membrane with photoreactive chemicals, the scientists found that each protein was surrounded by a ring of stacked lipids and – surprisingly –  that these lipids were shared with neighbouring membrane proteins, thus effectively gluing proteins together in organised patterns.

These patterns span the entire bacterial surface and include hexagonal lattices reminiscent of those used to strengthen protective body armour.

“This work explains how the different building blocks of the bacterial outer membrane stick together,” Professor Hoogenboom explains. “Every protein appears connected to other proteins in the membrane by a network of lipids, creating cellular armour plating that researchers will need to take into account when designing antibiotics that cross or disrupt the membrane.”

The work was supported by the European Research Council, the Wellcome Trust, the Medical Research Council and the Engineering and Physical Sciences Research Council.

 

Links

• Research article in Science Advances
• Sharpest images ever of living bacteria recorded by UCL researchers in 2021  
• Professor Bart Hoogenboom’s academic profile  
• London Centre for Nanotechnology
• UCL Physics & Astronomy  

Images

• Top: Microscopic view of the E. coli outer membrane, in which trimers of proteins are marked by purple disks. These trimers form a network in which other (monomeric) proteins are embedded. The scale bar (bottom right) is 50 nanometres. Credit: Dr Georgina Benn (London Centre for Nanotechnology, UCL).
• Bottom: Magnified view of the E. coli outer membrane showing hexagonal clustering of proteins (red/green), alongside body armour for comparison. The black background represents lipids that are shared between neighbouring proteins. Credit: Dheeraj Prakaash and Professor Syma Khalid (Department of Biochemistry, University of Oxford).

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