Bacterial Responses to Candidate Antimicrobials from Historical Pharmacopeias

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project:
From the Black Death to modern "superbugs" like MRSA, troublesome microbes have caused illness and death throughout human history. Historical medical texts provide a wealth of information on natural products and remedies that have shown activity against a wide range of pathogens, including antibiotic-resistant bacteria such as MRSA. Could these provide new antibiotics? My supervisor's lab has identified two promising historical remedies, Bald's Eyesalve (a combination of garlic, onion, wine and bile) and the other a combination of stinging nettles, salt and vinegar.
Both have very different natural products, but the common theme is their efficacy is dependent on the combination of ingredients. I will take an interdisciplinary approach to discover why this is the case and assess the clinical potential of the molecules present in these mixtures. I will use skills and techniques from the life sciences to understand how bacteria react to these natural products, (fundamental microbiology, confocal microscopy) and how they might evolve resistance to them (bioinformatics tools). I will use analytical chemistry techniques to try to identify biologically active compounds within natural products. I will learn and use a range of statistical approaches to analyse the data I collect. My work could help to identify new molecules that, in the future, could be turned into drugs to treat antibiotic-resistant infections. Ultimately, I will integrate skills from life sciences and chemistry to produce research geared to translational medicine.
I will join a wider "AncientBiotics" consortium including historians, immunologists, microbiologists and medicinal chemists allowing me to develop skills in team working and cross-disciplinary communication. Previous work has drawn significant media attention and led to public commination and outreach work, allowing me plenty of opportunities to get involved in communicating my work and its impact to a range of audiences.

Publications

10 25 50
 
Description Chemical Analysis of "Ancientbiotic" - The University of Warwick 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided preliminary chemical data and analysis. We have provided the biological activity of the samples and their fractions.
Collaborator Contribution The University of Nottingham has contributed expertise, analytical equipment and data analysis software.
Impact This collaboration is inter-disciplinary, with biologist and analytical chemists working together to understand a complex mixture.
Start Year 2019
 
Description British Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact British Science Week is an annual celebration of science, technology, engineering and maths that features a range of fascinating, entertaining and engaging national, regional and local events across the UK.

We had a stall here that was based around microbes forming communities and how this makes them harder to treat. The event was aimed at a younger audience, with multiple interactive activities. 1) Lego - bacteria like to build up communities, they build houses, cars etc. Can the children help build our community up throughout the day? Took progress pictures throughout.
Slime - sometimes bacteria produce a slime to help they survive. This slime makes it much harder for our medicines to reach them. We illustrated this with beads (our bacteria) with or without hair gel (a biofilm) on. Children had to shoot the beads off with a water pistol (the medicine) - much easier without the slime.
Giant kerplunk - the balls (medicine) can't get through to the bottom (where the infection is) to treat it because there are "straws" in the way (the biofilm). We need to break down the biofilm (remove the straws) to get the medicine to the infection to kill it.
Year(s) Of Engagement Activity 2019
 
Description Public science evening 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 50 - 100 members of the public intended our evening.
The evening was used to raise awareness of antimicrobial resistance and that looking into the history of medicine / the past may provide answers.
The event started with different stalls presenting their work, and audinece approaching and asking questions etc.
The event then had a series of short talks, with various PIs discussing the issues and how their work is attempting to answer some of these issues. The event ended with a discussion panel. Questions that had been submitted throughout the event were address, in addition to any further questions from the audience.
Year(s) Of Engagement Activity 2019
 
Description Public science evening - "The Rise of the Superbugs: Will your next infection kill you?" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact 50 - 100 members of the public intended our evening.
The evening was used to raise awareness of antimicrobial resistance and the risks associated with it.
The event started with different stalls presenting their work, and audience approaching and asking questions etc. The event then had a series of short talks, with various PIs discussing the issues and how their work is attempting to answer some of these issues. The event ended with questions from the audience.
Year(s) Of Engagement Activity 2019
URL https://warwick.ac.uk/about/publicengagement/events/scienceonthehill/pastevents/AMR