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Scientists design new tool to help fight antibiotic resistance

Posted by on October 21, 2015

By Ellie Welch, science media researcher at ISIS Neutron and Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory.

Structure of the complete outer membrane model (Credit: Luke Clifton)

The first working model of a bacterial membrane has been created by researchers at the ISIS Neutron and Muon Source in collaboration with Newcastle University. This model of E. coli will be an important tool in drug design and developments, especially for antibiotics.

Gram negative bacteria, such as E. coli, have an additional outer membrane which acts as a protective shield against antibiotics. As most antibiotics have to break through the bacterial membrane to get inside and work, an additional barrier means bacteria like E. coli are a major cause of antibiotic resistant infections. However, the size and exterior of the outer membrane make it difficult to study its structure and behaviour.

“We have built, for the first time, a working bacterial membrane” says lead author Professor Jeremy Lakey, Newcastle University.  “Now we can find out how the membrane works and design drugs to cross it.”

The research, supported by the Wellcome Trust, has been published as a ‘Hot Paper’ in the journal Angewandte Chemie International Edition, and highlighted in Nature Chemical Biology.

The model, which is only 1/10,000th the thickness of a sheet of A4 paper, was constructed at the ISIS Neutron Facility in Oxfordshire. Using a combination of neutron scattering and isotopic labelling experiments, scientists were able to confirm not only the structure but also the thickness, density and chemical make-up of the model.

ISIS scientist, Luke Clifton in one of the Biological Support Laboratories at the ISIS Neutron and Muon Source (Credit: STFC)

“Neutron scattering allows us to resolve complex structures composed of mixtures of biomolecules,” says joint author and ISIS scientist, Dr Luke Clifton. “Using isotopic labelling, we were able to determine the relative positions of the different components in the model.”

The model behaves just like a living bacterium’s membrane, and opens up exciting opportunities for future research in the fight against antibiotic resistance.

Find out more on the Science and Technology Facilities Council website.

Professor Mike Ferguson CBE FRSB, University of Dundee commented:
“Antimicrobial Resistance is a huge problem, particularly for gram negative bacteria (the focus of this research). Tackling AMR requires multi- and inter-disciplinary approaches to better understand fundamental bacterial physiology, and thus to identify new therapeutic approaches. This elegant new work allows researchers to see how chemical agents (small molecules and proteins) affect the outer membrane structure of bacteria and thus how they might disrupt it, and potentially render resistant bacteria sensitive to therapeutic agents.”

The Royal Society of Biology is a part of the Learned Society Partnership on Antimicrobial Resistance (LeSPAR) – a group of learned societies that are focused on taking action, championing best practice and raising awareness of the global challenge of antimicrobial resistance.

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