Bioprospecting plant extracts (and marine biota) for anti-C. difficile potential

1st July 2017 - ongoing

Status: Active

Specialism: Lower GI, Clostridium difficile.

Team: Dr Tanya Monaghan.

Natural products are an unsurpassed source of chemical diversity and an ideal starting point for any screening programme for pharmacologically active small molecules, occupying an increasingly important role in drug discovery. The aim of this pump-priming research is to form a multidisciplinary UK-Chinese partnership comprising gastroenterologists, molecular microbiologists, pharmacists, and chemists to identify plant extracts with potential anti-bacterial activity against Clostridium difficile infection. Using broth microdilution assays and high-throughput robotic liquid handling facilities, we will initially screen >1800 plant extracts derived from the Natural Product Library held at Robert Gordon University in Aberdeen against toxigenic C. difficile. This library consists of de-tannified extracts from 5000 plants representing 95% of plant families, and is therefore one of the most biodiverse and hence chemically diverse collections available for screening in existence. Candidate extracts inhibiting/reducing bacterial growth will be subsequently tested in Caco-2 transwell and Vero cell cytotoxicity assays. In follow-on studies, hit extracts reducing infectivity without cytotoxicity will be tested in vitro against multiple intestinal bacterial species and several strains of C. difficile for bacterial selectivity, prior to undertaking bioassay-guided fractionation studies and isolation and structure elucidation of the active compounds. We anticipate that the library can be used for biological research and drug discovery by other research groups within the NDDC BRU.

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Dr Tanya Monaghan Dr Monaghan came to Nottingham in 2006 and took up the position as the first NIHR Academic Clinical Fellow in Gastroenterology. Alongside clinical training, she worked in the laboratory of Professor Yash Mahida. She was subsequently awarded a Wellcome…
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