Wednesday, 22 January 2020
Researchers have found how an antibiotic used to treat a debilitating gut infection stays put inside the body giving it time to effectively treat the problem, a discovery that will pave the way for the development of more effective antibiotic treatments to fight superbugs.
PE (pseudomembranous colitis) is a debilitating inflammation of the colon caused by infection with the microbe Clostridium difficile (andsometimesStaphylococcus aureus). The sugar- or carbohydrate-containing antibiotic known as vancomycin is taken by mouth to kill the infecting microbe.
To be effective, vancomycin needs to stay in the GI tract (gut) close to where it is needed and not be diluted away or lost through the lining of the gut and into the bloodstream. A multi-disciplinary team of scientists at the Universities of Nottingham and Leeds have now shown this ‘staying put’ mechanism is precisely what happens and that it can occur in an unexpected way.
Forming a formidable barrier
The research, published today in Scientific Reports shows that protein-carbohydrate molecules of the gut called mucins provide a formidable barrier helping to prevent the drug escaping using a unique mechanism of formation of large molecular complexes or clumps. The antibiotic and mucins join together to form a mucoadhesive complex, likely trapping the antibiotic within large complexes. It is the trapped vancomycin which the scientists believe may lead to delayed transit of the antibiotic leading to prolonged exposure of the antibiotic to the infectious C. difficile.
Vancomycin is a precious ‘last-line’ antibiotic in the clinician’s arsenal of therapies to fight several important pathogens including MRSA, pneumonia, as well as C. difficile. The clumping effect with gut mucins revealed in our study not only gives new information about what may happen when the antibiotic is given orally, but might also provide new insights into its behaviour when infused into patients suffering from other life-threatening infections.
The findings also fit with other studies which show that oral vancomycin produces high levels of vancomycin resistance amongst some gut bacteria (VRE), contributing to the generation of antimicrobial resistance (a serious concern); the clumping/ complexation phenomenon may therefore provide the first explanation of a mechanism by which this VRE generation occurs. But the benefits of taking oral vancomycin at the right time and when appropriate still outweigh any negative generation of antimicrobial resistance, and the study highlights that it is wise to take vancomycin when your GP advises it is good to do so.
The antibiotic vancomycin is a truly remarkable molecule – a drug with its own mucoadhesive or sticky property which slows its transit through the gut right down giving maximum therapeutic effect and minimizing unused vancomycin being returned to the environment. If scientists are going to win the fight against anti-microbial resistance, joint institutional and interdisciplinary approaches like this successful one are going to prove crucial.
Notes to editors:
About the University of Nottingham
Ranked 32 in Europe and 16th in the UK by the QS World University Rankings: Europe 2024, the University of Nottingham is a founding member of the Russell Group of research-intensive universities. Studying at the University of Nottingham is a life-changing experience, and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement.
Nottingham was crowned Sports University of the Year by The Times and Sunday Times Good University Guide 2024 – the third time it has been given the honour since 2018 – and by the Daily Mail University Guide 2024.
The university is among the best universities in the UK for the strength of our research, positioned seventh for research power in the UK according to REF 2021. The birthplace of discoveries such as MRI and ibuprofen, our innovations transform lives and tackle global problems such as sustainable food supplies, ending modern slavery, developing greener transport, and reducing reliance on fossil fuels.
The university is a major employer and industry partner - locally and globally - and our graduates are the second most targeted by the UK's top employers, according to The Graduate Market in 2022 report by High Fliers Research.
We lead the Universities for Nottingham initiative, in partnership with Nottingham Trent University, a pioneering collaboration between the city’s two world-class institutions to improve levels of prosperity, opportunity, sustainability, health and wellbeing for residents in the city and region we are proud to call home.
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