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Title: Exploring marine sponges as a source of novel chemical entities for drug development
Author: Hatton, Christopher Martin
ISNI:       0000 0004 5359 8560
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2015
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Antibacterial resistant infections are one of the most challenging problems affecting healthcare and have developed through the overuse of antibiotics and a shortage of new treatments progressing to market. Natural products are the initial source of most antibiotics currently available and marine sponges are a known resource of novel antibacterial compounds; although well-­‐studied marine sponges found in UK waters have been scarcely explored. An examination of the chemical research on sponges identified previously unstudied species for collection in both Greece and Wales. Sequential solvent gradient extraction was optimised, to best exploit the material collected, providing three crude extracts for each sponge collected. A significant difference was observed between the chemical composition of sponges collected from Greece and Wales. An efficient antimicrobial assay was developed to screen each extract against clinically relevant organisms; allowing the direct identification of activity on an eluted thin layer chromatography plate. This overlay data was used for detailed chemical analysis using high performance counter current chromatography, with some separated fractions displaying greater activity towards the bacterium methicillin resistant Staphylococcus aureus (MRSA) than vancomycin. The parent masses of compounds responsible for activity were identified by directly coupling the overlay assay data to mass spectrometry, identifying multiple novel parent masses. Dereplication of samples was completed using the database MarinLit and the construction of a molecular network to compare fragmentation patterns in mass spectra. Bacterial cultivation from Welsh sponge samples isolated 18 antibacterial strains, which were identified using 16S rRNA analysis. Four of these strains were previously uncultured. Chemical analysis was also completed, on two unstudied strains, identifying further active novel parent masses, with no parent mass crossover to the host sponge. Overall, this investigation concluded that marine sponges are excellent source of novel antibacterial compounds, which can display activity against clinically relevant bacteria equivalent to current treatments.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General) ; RM Therapeutics. Pharmacology