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 Gram-positive 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.
Highlights
Novel antimicrobials are urgently needed to combat drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections
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 g roup9,10) and will be expedited if early discovery work on leads takes into account the inherent difficulties of treating biofilm-associated infections[6,11]
No single ingredient recaptures the anti-biofilm activity of Bald’s eyesalve, and the presence of allicin cannot fully explain the ability of the whole mixture to kill either planktonic cultures grown in host-mimicking medium, or biofilms grown in an in vivo-like model of a soft tissue wound
Summary
Novel antimicrobials are urgently needed to combat drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. No single ingredient recaptures the anti-biofilm activity of Bald’s eyesalve, and the presence of allicin cannot fully explain the ability of the whole mixture to kill either planktonic cultures grown in host-mimicking medium (synthetic wound fluid), or biofilms grown in an in vivo-like model of a soft tissue wound. We tested one example pair of ESO and ESL variants (batch 6) against a panel of twelve clinical isolates of S. aureus grown in the synthetic wound biofilm model.
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