Written by Joyce Smith, BS. This study demonstrates that natural antimicrobials may be more effective, particularly against bacterial biofilms, when used in combination rather than alone.
It is estimated that by 2050 ten million people per year will succumb to antimicrobial resistant infections 1,2. Biofilm-associated infections are of particular concern. Biofilms are communities of bacteria that produce a protective extracellular matrix which renders them impervious to antibiotic treatment 3. Biofilms also require a far greater use of antibiotics compared to the same bacteria growing planktonically (as individual free-floating cells) 4. Most antibiotics that are used today are derived from natural compounds; however, antibiotics derived from a combination of natural ingredients might be more effective against pathogenic bacteria, especially those that greatly impact on our health and economy such as the ESKAPE group 5,6. (ESKAPE is an acronym for the group of bacteria that encompasses both Gram-positive and Gram-negative species, and is made up of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).
Building on previous research done by the University of Nottingham regarding the use of medieval remedies to treat MRSA, the researchers from the School of Life Sciences at University of Warwick 7 reconstructed a 1,000-year-old medieval remedy (Bald’s eyesalve). Containing a combination of natural ingredients (onion, garlic, wine, and bile salts), Bald’s eyesalve has antibacterial activity with minimal damage to human cells and, according to the Bald’s Leechbook manuscript, was used to successfully treat eye infections.
In this study, the Warwick Group 7 investigated the anti-biofilm activity of Bald’s eyesalve, hoping their research might lead to the discovery of effective natural antimicrobials, particularly against the hard-to-treat antibiotic-resistant biofilms that infect diabetic foot ulcers today. After successfully reconstructing the formula, they tested the bactericidal activity of Bald’s eyesalve against a panel of clinically relevant strains of ESKAPE pathogens in planktonic culture and against wound model biofilms of a subset of these strains that commonly cause chronic wound infections: gram-negative Pseudomonas aeruginosa PA14, Acinetobacter baumannii clinical isolate, Enterobacter cloacae, Stenotrophomonas maltophilia and gram-positive and Staphlococcus aureus Newman, Staphlococcus aureus USA300, Staphlococcus epidermidis and Streptococcus pyogenes.
Researchers found that Bald’s eyesalve eradicated planktonic cultures of all gram-negative and gram-positive bacteria and even caused a 4-log reduction in viable cell counts in the especially problematic methicillin-resistant S. aureus USA300 (MRSA); however, variable or no activity was seen against biofilm cultures of these isolates in the synthetic soft tissue wound model. However, in the same wound model, Bald’s eyesalve significantly reduced viable cell counts in biofilms of S. epidermidis and MRSA and completely eradicated biofilms of S. aureus Newman, A. baumannii and S. pyogenes.
Secondly, researchers assessed whether any individual ingredient or the sulphur-containing compound allicin (from garlic) could explain this bacteriocidal activity. They found that the presence of garlic in the Bald’s eyesalve mixture contributed to the activity against planktonic cultures, yet, when garlic was tested alone, it had no activity against the biofilms. In fact, running tests with one of the four ingredients alternately missing revealed that all four ingredients were necessary for the potent anti-biofilm activity of Bald’s eyesalve.
This study demonstrates the importance in research of focusing on the potential of potent anti-biofilm cocktails rather than isolating single compounds and possibly overlooking the synergistic and anti-biofilm potential of natural antimicrobial combinations. Viewing them from this perspective may expedite the search to create new antibiotics from botanicals that have the potency to treat difficult biofilm infections.
Source: Furner-Pardoe, Jessica, Blessing O. Anonye, Ricky Cain, John Moat, Catherine A. Ortori, Christina Lee, David A. Barrett, Christophe Corre, and Freya Harrison. “Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients.” bioRxiv (2020).
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, http://creativecommons .org/licenses/by/4.0/.
Click here to read the full text study.
Posted August 18, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- O’Neill, J. Tackling drug-resistant infections globally: final report and recommendations. Review on antimicrobial resistance; 2016.
- Wright GD. Opportunities for natural products in 21(st) century antibiotic discovery. Nat Prod Rep. 2017;34(7):694-701.
- Penesyan A, Gillings M, Paulsen IT. Antibiotic discovery: combatting bacterial resistance in cells and in biofilm communities. Molecules. 2015;20(4):5286-5298.
- Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37(6):1771-1776.
- Tacconelli E, Carrara, E., Savoldi, A., Kattula, D. & Burkert, F. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. 2019.
- Pendleton JN, Gorman SP, Gilmore BF. Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther. 2013;11(3):297-308.
- Furner-Pardoe J, Anonye BO, Cain R, et al. Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients. Sci Rep. 2020;10(1):12687.
