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Title: Phytochemical and biological investigation of immature conifer cones for antibacterial and modulatory activity against multidrug-resistant and methicillin-resistant Staphylococcus aureus
Author: Smith, Eileen Catherine Jean
ISNI:       0000 0004 2672 068X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2006
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Antibiotic resistance by pathogenic bacteria is a major problem both in hospitals and in the community. Of particular concern is methicillin-resistant Staphylococcus aureus (MRSA), many strains of which have acquired resistance to most antibiotics. Another mode of resistance is by means of an efflux pump and many S. aureus strains have acquired pumps which confer multidrug-resistance by effluxing many different compounds out of the cell. There is an urgent need to find new antibacterials and new ways to fight these resistant strains. The rationale for this study is that since cones are essential for reproduction in conifers, the immature cones are likely to contain compounds which protect against microbial invasion. Initial screening of cones from several conifer species identified anti-staphylococcal activity, which was greatest in the hexane extracts. Bioassay guided fractionation and structure elucidation using 1-D and 2-D NMR yielded several active diterpenes from Chamaecyparis lawsoniana, Chamaecyparis nootkatensis and Pinus nigra. These compounds showed activity (2 - 64 μg/ml) against multidrug-resistant and effluxing S. aureus clinical isolates, and against epidemic MRSA strains EMRSA-15 and -16, which are the major strains found in UK hospital MRSA bacteraemias. Some of the isolated diterpenes also demonstrated activity as potentiators of antibiotic activity. Ferruginol restored oxacillin sensitivity in EMRSA-15, and moderate activity in potentiating antibiotic activity against effluxing strains was also observed for ferruginol and totarol. Efflux inhibition assays suggested that these compounds were weak efflux pump inhibitors. This study demonstrates that compounds from immature conifer cones have good antibacterial activity and some modulatory activity against resistant strains of S. aureus. These compounds are worthy of further investigation, particularly as plants produce compounds which clinically relevant bacteria are unlikely to have previously encountered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available