Antibacterial activity and mechanism of action of semi-synthetic cocktail formulated from the Bald's eyesalve

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Antimicrobial-resistant infections, especially those associated with biofilms, continue to create a global health challenge due to the high mortality and economic loss associated with drug-resistant infections. Chronic wound infections and lung infections in people with cystic fibrosis both pose annual economic burdens of $281Bn and $7509Bn respectively. Prior to the discovery of antibiotics, infections were often treated with combinations of different natural products. Our lab has identified a medieval remedy called "Bald's eyesalve" which was used to treat eye infections. This remedy has shown broad-spectrum activities against planktonic and biofilm forms of wound and lung pathogens. Starting from preliminary data already obtained in our lab, our plan is to formulate a semi-synthetic cocktail comprising only the compounds that give this complex recipe its biological activity. We will narrow down the complex remedy to a set of semi-synthetic or fully synthetic mixtures of natural products, and test the ability of these cocktails to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa in wound and lung biofilm models. This will allow us to formulate a final, chemically defined cocktail that could be used to treat infections. Furthermore, we will determine the mechanism of action of our cocktail against the two pathogens mentioned. We will also look to enhance the activity of our cocktail by combining it with other antimicrobials, and to assess its safety profile for therapeutic use. This project will pave way for a new approach to testing the antimicrobial activity of natural products through the combination of different bioactive compounds in their natural and synthetic forms.