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Title: Antiplasmid and antimicrobial activities of synthetic and natural products from selected medicinal plants
Author: Mbaebie Oyedemi, B. O.
ISNI:       0000 0004 5367 0737
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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This PhD thesis is part of ongoing project to identify plant natural products and selected synthetic compounds that possess antimicrobial properties; and are able to promote plasmid loss or interfere with bacterial conjugation. The conjugative broad host plasmids investigated include PKM101 (Inc N), TP114 (Inc I2), PUB307 (Inc P), and low- copy number plasmids: R6K (Inc X), R7K (Inc W) and R1-drd-19 (Inc F11). They represented the incompatibility plasmid groups that are currently associated with gross dissemination of antibiotic resistance in bacteria. A series of plant extracts evaluated at sub-inhibitory concentration of 100 mg/L, were shown to inhibit bacterial plasmid conjugation and their active constituents were isolated and characterised. Mallotus philippinensis yielded rottlerin and red compound, with good to moderate antibacterial activity against multidrug resistant Staphylococcus aureus strains, and had a broad range inhibition against the resistant plasmids. Investigation of extracts from the resin of Cannabis sativa L. identified tetrahydrocannabinolic acid (THCA) and cannabinolic acid (CBNA) which in addition to two synthetic cannabinoids: cannabigerol and olivetol inhibited the conjugal transfer of TP114 between E. coli strains. The antiplasmid activities of Δ9-THC, CBN, CBD, significantly reduced the transfer of amoxicillin–resistance conferring PKM 101. Methanolic extract from the dried fruits of Evodia rutaecarpa yielded evodiamine, rutaecarpine and naturally-isolated sucrose. Rutaecarpine was the most active alkaloid against NorA-expressing SA1199B and XU212 strain expressing TetK efflux mechanism. Evodiamine and sucrose had lesser antibacterial effect as well as low level of inhibition against the plasmids. Rutaecarpine and evocarpine remarkably reduced the transfer frequency of PKM 101, showing a high 2 level effect of inhibition by the compound. The bioassay-guided analysis of Capsicum annuum L. yielded capsaicin and dihydrocapsaicin (DHC) which demonstrated moderate antibacterial activities but inhibited conjugal transfer of R-plasmids actively. Capsaicin exhibited a broad range antiplasmid activity while DHC showed selective inhibition. The effect of synthetic compounds that were assessed: ferulenol, 6-gingerol and 6-shogoal were twice as effective against the transfer of PKM 101, TP114 and PUB307 compared to capsaicin, while nonivamide had no remarkable activity. With the exception of promethazine, capsaicin and dihydrocapsaicin that showed some interaction with DNA due to decreased fluorescence which suggests binding, the rest of the compounds: rottlerin, red compound, ferulenol, evocarpine, rutaecarpine, 6-gingerol, 6-shogaol and nonivamide did not bind to DNA. This may indicate other probable mechanism of antiplasmid action of the compounds. Together, some of these compounds were notable for their dual properties: robust antistaphylococcal activity and a broad host range antiplasmid effect, and are reported for the very first time. Such potentials are valuable in the discovery of next generation antimicrobial drugs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available