Year: 2013
Type: dissertation
Abstract: The emergence and spread of antibiotic resistance hampers effective treatment of bacterial \ninfections. This is particularly the case for infections involving a biofilm component, as \nthe activity of existing antibacterial drugs against these surface-attached communities is \nlimited. The work presented in this thesis sought to identify and characterise compounds \nwith antibacterial and antibiofilm activity against the important pathogen, Staphylococcus \naureus. \nAntistaphylococcal activity was assessed for 16 antioxidants that are used in cosmetics, \ntraditional medicines or as food additives, and which have been reported previously \nto have some antibacterial activity. Initial experiments with tert-butylhydroquinone \n(TBHQ) showed that activity that had previously been ascribed to the antioxidant, \nwas a consequence of its conversion to tert-butylbenzoquinone (TBBQ) under culture \nconditions. TBBQ displayed innate bactericidal activity against S. aureus that was \neffected through perturbation of the bacterial membrane. The other antioxidants also \ninhibited staphylococcal growth through perturbation of the cytoplasmic membrane, and \ncompounds that displayed selective action against bacterial membranes were identified. \nOf the agents with bacterial specificity, TBBQ, celastrol and nordihydroguaiaretic acid \n(NDGA) also eradicated staphylococcal biofilms; a rare property amongst antibacterial \nagents. Although these antioxidants exhibited a similar membrane-damaging mode of \naction, their mechanisms of antibiofilm activity differed. TBBQ eradicated preformed \nbiofilms through sterilisation of slow-growing and persister cell populations, whilst \ncelastrol and NDGA caused physical disruption of the biofilm. All three antioxidants \nacted synergistically with gentamicin against biofilms, eradicating surface attached \npopulations at concentrations that did not cause irritation or visible damage to a human \nskin equivalent. \nThe potent and selective antibacterial activity, and low resistance potential upon extended \nsubculture, suggest that these compounds could be used topically in combination with \ngentamicin to treat infected wounds.
Author: Nicola Ooi
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2607431809