Oluwatuyi, Moyosoluwa Olurele;
(2004)
Natural product modulators of multidrug resistance (MDR) in Staphylococcus aureus.
Doctoral thesis (Ph.D.), University College London.
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Abstract
This PhD thesis is part of an ongoing project to identify plant natural products that modify resistance in multidrug resistance (mdr) Staphylococcus aureus. A series of plant extracts were evaluated, shown to possess modulating activity against MDR strains and their active constituents were isolated and characterised. Lycopus europaeus (Lamiaceae) yielded seven compounds with moderate modulating activity against tetracycline (TetK) and erythromycin (MsrA) resistant S. aureus strains. Two of these compounds are new. Investigation of extracts from the leaves of the desert tree Prosopis juliflora (Fabaceae) yielded six compounds showing very potent antibacterial and modulation activity against a panel of mdr S. aureus strains including the norfloxacin resistant strain (NorA). Two of these are novel and possesses a highly unusual four-membered ring system directly bound to a quaternary nitrogen of a pyridine ring. Bioassay-guided fractionation of the chloroform extract of Rosmarinus officinalis (Lamiaceae) yielded four phenolic diterpenes and one flavonoid. These compounds showed antibacterial and resistance modifying activity in vitro against two strains of S. aureus possessing the TetK and MsrA multidrug efflux mechanisms. Extracts from the root of the Chinese plant Cynanchum paniculatum (Asclepiadaceae) yielded two compounds. Both demonstrated a modest resistance modifying activity against the TetK, MsrA and NorA multidrug efflux mechanisms. A phytochemical investigation of the methanolic extract of Anabasis setifera (Chenopodiaceae) was carried out and this yielded two compounds. These compounds were shown to work in synergy with antibiotics (which have previously been rendered ineffective against these pathogens) to reduce their effective minimum inhibitory concentration (MIC) against strains of S. aureus expressing the multidrug efflux pumps thereby extending their useful lifespan. These data highlight the potential of plants as a source of bacterial resistance modifying agents and can be a first step towards overcoming the emergence of resistant pathogens.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Natural product modulators of multidrug resistance (MDR) in Staphylococcus aureus. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10121809 |
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