A 1000-year-old medieval remedy with anti-biofilm activity requires a combination of multiple ingredients
The Microbiology Society is undertaking a project entitled A Sustainable Future as part of our 75th Anniversary, which aims to highlight the Sustainable Development Goals (SDGs) to our members and empower them to use their research to evidence and impact the goals. Earlier this year, we put a call out to our members to submit case studies in the following three areas: antimicrobial resistance, soil health and the circular economy.
This case study is written by Dr Blessing Anonye, who is a Lecturer in Medical Microbiology at the University of Central Lancashire, and Jessica Furner-Pardoe, who is a PhD student at the University of Warwick. They are both members of the Microbiology Society. It focuses on antimicrobial resistance; a naturally occurring process, whereby micro-organisms (bacteria, viruses, fungi and parasites) can change and adapt over time, either by modifying the target of the antimicrobial, or by developing and exchanging resistance genes.
What are the challenges/needs that this research addresses?
New antimicrobials are urgently needed to fight bacterial infections which have become resistant to antibiotics. Antimicrobial resistance (AMR) poses a serious threat to human health, as in the absence of effective antimicrobials, common bacterial infections amenable to treatment would become untreatable. Routine surgical operations requiring prior usage of antibiotics will be affected, and this is particularly true for those with a weakened immune system.
It is no longer news that estimates of 10 million people per year are likely to be killed by 2050 globally if we can’t find or develop new antimicrobials (1). This rise in AMR, coupled with the lack of development of new antibiotics, has prompted research into the use of alternative agents as antimicrobials. An example of an agent that has the potential to treat bacterial infections, is a plant-derived mixture used in early medieval England known as ‘Bald’s eyesalve’, for the treatment of styes or eye infections (2).
What findings and solutions were provided by this research?
Through collaboration with a specialist in medieval English language (Dr Christina Lee, University of Nottingham, UK), our team previously showed that a 1000-year-old remedy (Bald’s eyesalve) used in the medieval period had antibacterial activity against the common bug Staphylococcus aureus which causes a range of diseases in humans (2).
In our current research, we went further to show the efficacy against several clinically relevant pathogens popularly referred to as the ‘ESKAPE’ group (3), some of which feature on the World Health Organization’s priority list of antimicrobials that are urgently needed (4). Our work demonstrated that Bald’s eyesalve could kill the bacteria when grown as planktonic cultures and in biofilms mimicking soft tissue infections (5).
The original translation of Bald’s eyesalve, requires the combination of onions, garlic, wine and bile kept for nine days, then strained prior to application. Interestingly, we found out that in order to achieve anti-biofilm activity, we needed to combine all ingredients as stated, as individual or single ingredients did not have the ability to kill bacteria growing as biofilms.
How can this research support the transition to a more sustainable future?
Plant based compounds are natural products that are readily available in the environment. Having an antimicrobial agent that is effective in treating antibiotic resistant bacteria will lead to a reduction in the associated cost of treating individuals with biofilm associated infections. For example, it is estimated that over £1 billion is spent yearly by the UK National Health Service to treat bacterial infections associated with biofilms (6). This would directly translate to savings and a more sustainable future, as the drugs can also potentially be utilised in veterinary medicine. More importantly death rates would be greatly reduced as less people would die of antibiotic resistant infections.
What is the future for research and innovation in this area?
There remains huge potential for research to determine the active components within Bald’s eyesalve that makes it so good at doing what it does. We already know that allicin, sourced from garlic, is partly responsible for the anti-biofilm activity, but we need to find other compounds that work in synergy to achieve this antibacterial activity. The pursuit of compounds, which when combined together have powerful antimicrobial properties, is a promising active area of research (7, 8).
For this research to be translated to the clinic, we need to ensure it is safe for human use. Recently, we have shown in several in vitro and in vivo models, the safety potential of Bald’s eyesalve (9). We need to move to the next step of performing clinical trials in healthy volunteers to assess its safety for topical use.
- O’Neill J. Tackling drug-resistant infections globally : final report and recommendations the review on antimicrobial resistance (2016).
- Harrison F, Roberts AEL, Gabrilska R, Rumbaugh KP, Lee C, Diggle SP.. A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. mBio 6:e01129-15 (2015).
- David M. P. De Oliveira, Brian M. Forde, Timothy J. Kidd, Patrick N. A. Harris, Mark A. Schembri, Scott A. Beatson, David L. Paterson, Mark J. Walker. Clinical Microbiology Reviews, 33 (3) e00181-19 (2020).
- Tacconelli, E. et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 18, 318–327 (2018).
- Furner-Pardoe, J., Anonye, B.O., Cain, R. et al. Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients. Sci Rep 10, 12687 (2020).
- Guest, J. F. et al. Health economic burden that different wound types impose on the UK’s National Health Service. Int. Wound J. 14, 322–330 (2017)
- Caesar, L.K., Cech, N.B. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Natural Product Reports 36, 869-888 (2019).
- Quave C. Antibiotics from nature: traditional medicine as a source of new solutions for combating antimicrobial resistance (2016). http://resistancecontrol.info/rd-innovation/antibiotics-from-nature-traditional-medicine-as-a-source-of-new-solutions-for-combating-antimicrobial-resistance/ Accessed 11th August 2020.
- Anonye, B. O. et al. The safety profile of Bald’s eyesalve for the treatment of bacterial infections. BioRXiv https://doi.org/10.1101/2020.04.23.041749 (2020).
About the authors
Dr Blessing Anonye is a Lecturer in Medical Microbiology at the University of Central Lancashire, and a Visiting Research Fellow at the University of Warwick. Jessica Furner-Pardoe is a PhD student at the University of Warwick. They are both members of the Microbiology Society. More details of their work can be found here.