Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

Abstract

Novel antimicrobials are urgently needed to combat drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Studying plants and other natural materials used in historical infection remedies may enable further discoveries to help fill the antibiotic discovery gap. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, known as 'Bald's eyesalve', and showed it had promising antibacterial activity. In this current paper, we have found this bactericidal activity extends to a range of Gram-negative and Grampositive wound pathogens in planktonic culture and, crucially, that this activity is maintained against Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes in a soft-tissue wound biofilm model. While the presence of garlic in the mixture can explain the activity against planktonic cultures, garlic has no activity against biofilms. We have found the potent anti-biofilm activity of Bald's eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections and underlines the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline. Widespread multidrug resistance of once-susceptible pathogens, combined with a lack of success in developing novel antimicrobials, has resulted in a looming crisis. Antimicrobial resistance leads to problematic infections, threatens the success of routine surgery and cancer treatments 1 , and is estimated to kill 10 million people per year by 2050 2,3. One particularly troublesome area is biofilm-associated infection. Biofilm infections are estimated to cost the UK's National Health Service over a billion pounds every year, with this cost only set to increase 4,5. Biofilms are communities of bacteria that produce a protective extracellular matrix and are especially persistent 6. Biofilm eradication often requires 100-1,000 times higher antibiotic concentrations to achieve clearance than the same bacteria growing planktonically (as individual free-floating cells) 7. In vivo, biofilms may essentially be completely impervious to antibiotic treatment 8. The path to overcoming biofilm infections requires a multifaceted response, including the discovery and clinical deployment of novel antimicrobials. This search for novel candidates must be directed towards those pathogenic bacteria with the highest health and economic impact (e.g. ESKAPE group 9,10) and will be expedited if early discovery work on leads takes into account the inherent difficulties of treating biofilm-associated infections 6,11 .

The Impacts of Ramadan Intermittent Fasting on Saliva Flow-Rate and Metabolic Data: A Systematic Review

“…Moreover, it would be great to compare the fasting saliva proteome with the non-fasting saliva, and to see if the fasting saliva can be a source of novel peptides that display health benefits ( 79 ). This will address the “myth/superstition” in medieval Europe where fasting saliva was used as a medicine ( 80 , 81 ).…”

Ethnopharmacological studies in 21st century Brazil: a systematic review

“…Given the current scenario of increasing microbial resistance to classic industrialized antibiotics, research into new antibiotics is of fundamental importance and ethnopharmacology can help in the development, or rediscovery, of new therapeutic approaches based on the synergism of phytochemical compounds, as discussed by Furner-Pardoe and collaborators (2020). According to these authors, the exploration of therapeutic approaches that are not based only on individual compounds, but on a mixture of natural compounds, can result in drugs with potent antimicrobial activity, as established in their study on the anti-biofilm activity of Bald's eye drops (Furner-Pardoe et al, 2020).…”

Probing the Comparative Bioefficacy of Allium sativum L. Bulb through Different Solvents

“…Prominent bactericidal effect of A. sativum may be due to either growth inhibitory effects of allicin or its ability of restraining microbial adherence on surface, an important stage in biofilm development. Moreover, biofilm gene expression is down-regulated by allicin, thiosulfate group that reacts with the numerous cellular proteins in pathogens, suggesting the therapeutic efficiency of A. sativum on settled biofilm [1,32,33].…”