Newcastle scientists show how hospital ‘superbug’ escapes antibiotics

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Newcastle researchers have become the first to reveal the ‘armor’ the hospital superbug C. difficile uses to protect itself from antibiotics.

The disease is now the most common superbug – and the new findings, including a stunning image of the bacteria’s structure, give hope to scientists studying how drugs could be developed to combat its antibiotic resistance.

Working with scientists across the country, a team from Newcastle University led by Dr Paula Salgado used an imaging technique called electron and X-ray crystallography to unveil a “narrow yet flexible outer layer to the bacteria that causes C. diff – and they compared it to chain mail.

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An article was published in the scientific journal Nature Communications – and in it, the researchers explain that they were able to explore the structure of the protein that protects the bacteria.

Dr Paula Salgado, a lecturer at Newcastle University, led the research. He said: “I started working on this structure over 10 years ago, it’s been a long and difficult journey but we’ve got some really exciting results.

“Surprisingly, we found that the protein forming the outer layer, SlpA, packs very tightly, with very narrow openings that allow very few molecules to enter the cells. The S layers of other bacteria studied up to present tend to have wider spaces, allowing larger molecules to penetrate.

“This may explain the success of C. diff in defending itself against antibiotics and immune system molecules sent to attack it.”

She said the new research gave scientists a “target” as they seek to produce better treatments for C. difficile – which can cause diarrhea and colitis at first, but can also be deadly.

“Excitingly, it also opens up the possibility of developing drugs that target the interactions that make up chain mail. If we break them, we can create holes that allow drugs and immune system molecules to enter the cell and kill it.

With antibiotic resistance identified as one of the top 10 threats to global public health by the World Health Organization – and C. difficile being resistant to all but three drugs – scientists believe the new findings may” allow the possibility of designing C. diff-specific drugs” to stop the disease in its tracks.

Dr Rob Fagan and Professor Per Bullough from the University of Sheffield carried out the electron crystallography work, while in Dr Salgado’s team at Newcastle Paola Lanzoni-Mangutchi and Dr Anna Barwinska-Sendra played a role key in the x-ray process.

The team’s work has now been illustrated by artist and science communicator Dr Lizah van der Aart.

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