Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.703344
Title: Antibacterial activity and mechanism of action of lipophilic antioxidants
Author: Ooi, Nicola Chooi Twan
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2013
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Abstract:
The emergence and spread of antibiotic resistance hampers effective treatment of bacterial infections. This is particularly the case for infections involving a biofilm component, as the activity of existing antibacterial drugs against these surface-attached communities is limited. The work presented in this thesis sought to identify and characterise compounds with antibacterial and antibiofilm activity against the important pathogen, Staphylococcus aureus. Antistaphylococcal activity was assessed for 16 antioxidants that are used in cosmetics, traditional medicines or as food additives, and which have been reported previously to have some antibacterial activity. Initial experiments with tert-butylhydroquinone (TBHQ) showed that activity that had previously been ascribed to the antioxidant, was a consequence of its conversion to tert-butylbenzoquinone (TBBQ) under culture conditions. TBBQ displayed innate bactericidal activity against S. aureus that was effected through perturbation of the bacterial membrane. The other antioxidants also inhibited staphylococcal growth through perturbation of the cytoplasmic membrane, and compounds that displayed selective action against bacterial membranes were identified. Of the agents with bacterial specificity, TBBQ, celastrol and nordihydroguaiaretic acid (NDGA) also eradicated staphylococcal biofilms; a rare property amongst antibacterial agents. Although these antioxidants exhibited a similar membrane-damaging mode of action, their mechanisms of antibiofilm activity differed. TBBQ eradicated preformed biofilms through sterilisation of slow-growing and persister cell populations, whilst celastrol and NDGA caused physical disruption of the biofilm. All three antioxidants acted synergistically with gentamicin against biofilms, eradicating surface attached populations at concentrations that did not cause irritation or visible damage to a human skin equivalent. The potent and selective antibacterial activity, and low resistance potential upon extended subculture, suggest that these compounds could be used topically in combination with gentamicin to treat infected wounds.
Supervisor: O'Neill, Alex ; Chopra, Ian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.703344  DOI: Not available
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