An interdisciplinary investigation into the antibacterial activity and chemical composition of the historical remedy Bald's eyesalve

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Abstract

The golden age of antibiotic discovery has granted us a respite from incurable infections. However, bacteria can become tolerant to antibiotics by forming biofilms, and they can evolve resistance to antibiotics, rendering them useless. Finding new antibiotics is difficult, but looking into historical medicine may provide some answers. This PhD project has conducted an interdisciplinary investigation into a 10th-century remedy, Bald's eyesalve. This remedy calls for crushed onion and garlic to be combined with wine and ox gall, and left to stand for 9 days. This remedy was previously shown to have potent activity against S. aureus. Here, I have identified that many steps in the recipe create a more active remedy, highlighting the potential scholar behind these texts. I demonstrate this activity extends to a broad range of planktonic cultures (S. aureus, including MRSA, A. baumannii (including multi-drug resistant strains), E. coli, P. aeruginosa, B. cenocepa- cia). Importantly, a subset of these strains grown as established biofilms in a synthetic wound model were also eradicated (S. au- reus, all A. baumannii and B. cenocepacia). A. baumannii was unable to develop resistance to the remedy, but became resistant to antibiotics (meropenem and ciprooxacin) within 35 days. Chemical analysis (HPLC) has identified that although allicin is responsible for the activity against planktonic cultures, it was significantly less active against biofilms than Bald's eyesalve. Further analysis (LC-MS/MS) identified a combination of allicin with an aqueous wine fraction work synergistically to eradicate these S. aureus biofilms. To conclude, a potent antimicrobial semi-synthetic cocktail containing allicin and aqueous wine components has been developed from the historical remedy Bald's eyesalve. Additionally, these results stress the importance of 1) including biofilm models when exploring natural products for the anti-biofilm pipeline; and 2) researching mixtures of natural products, rather than isolated compounds, may generate potent therapies.

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