Drug discovery

The initial aim of this whole initiative was to identify new antibacterial compounds which could be used to combat hospital superbugs and our starting point was honey.

Honey possesses therapeutic properties which are the result of a range of factors including high sugar content, low pH, hydrogen peroxide and bee-derived peptides. Honey also contains antimicrobial phytochemicals which represent a rich source of leads for the development of drugs for the treatment of microbial infections.

Honey samples donated by UK beekeepers (217) and Manuka samples (3) were screened for the presence of novel antibacterial compounds by determining activity against methicillin resistant Staphylococcus aureus (MRSA) using optimised agar well diffusion and broth microdilution assays. The majority (92%) of the honeys showed inhibitory activity. Identification of unknown factors was performed by neutralising antibacterial honey components previously described in the literature.

Results

Of the samples screened four samples were found to contain potentially novel antibacterial compounds.

The pollen present in honey represents a record of the plants which contributed to the making of the honey and may be the source of specific antibacterial factors. For this reason pollen was extracted from honey samples which demonstrated high levels of antimicrobial activity. Microscopic and DNA metabarcoding (454 and Illumina) analysis was performed. Plant species identified with DNA metabarcoding provided superior discrimination and greater repeatability.

Key species identified in the antibacterial samples included woodruff (Galium odoratum), bluebell (Hyacinthoides non-scripta) and dandelion (Taraxacum officinale).

Extracts from active honeys and characterised plants demonstrated antibacterial activity against MRSA, E. coli and P. aeruginosa using broth based methods and thin layer chromatography (TLC) bioautographic overlay methods.

Activity-guided characterisation using a TLC/mass spectrometry (MS) interface and high performance liquid chromatography (HPLC) was performed.

Compounds identified using these approaches included known pinobanksin derivatives and unknown compounds suggesting that the plants may be the original source of active compounds.

Next steps

Work is in progress to further characterise these compounds and to assess there utility as next generation antibiotics.

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