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dc.contributor.advisorBrown, Samen
dc.contributor.advisorFitzgerald, Jonathanen
dc.contributor.authorAllen, Richard Charlesen
dc.date.accessioned2017-12-20T15:41:12Z
dc.date.available2017-12-20T15:41:12Z
dc.date.issued2016-06-28
dc.identifier.urihttp://hdl.handle.net/1842/25789
dc.description.abstractBacterial infections are an increasing cause for concern as resistance spreads to the majority of our front line antibiotics. To counter antibiotic resistance, new treatment regimens and drug targets are being investigated, including directly targeting bacterial virulence (pathogen-induced harm to the host), and therapies which target resistance mechanisms. The outcome of successful treatment with these compounds is not always killing or halting growth of bacteria, therefore selection for resistance to these types of therapeutics is complex. This complexity is increased by the secretion of many virulence factors, meaning their effects are shared with neighbouring individuals. In addition virulence factors show high phenotypic plasticity due to regulation by processes like quorum sensing (QS), which further complicates treatments targeting virulence, or the regulatory processes themselves. Using the example of quorum sensing inhibitors this study shows the importance of understanding the function and ecology of targeted virulence factors, to predict the selection for resistance to anti-virulence drugs. Later chapters elaborate on this to show how quorum sensing control affects selection on secreted virulence factors. The use of anti-virulence drugs as adjuvants is discussed, with a study showing that the interaction between QS inhibition and translation inhibitors is dependent on the environment. The selection for resistance to combinations of antibiotics and adjuvants is investigated using co-amoxiclav as an example, showing that treatment with high doses of adjuvant are robust to the evolution of resistance.en
dc.contributor.sponsorNatural Environment Research Council (NERC)en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionAllen RC, Popat R, Diggle SP, Brown SP. (2014). Targeting virulence: can we make evolution-proof drugs? Nat Rev Micro 12: 300–308.en
dc.relation.hasversionAllen RC, McNally L, Popat R, Brown SP. (2016). Quorum sensing protects bacterial cooperation from exploitation by cheats. ISME J Advanced online publication.en
dc.subjectantibioticsen
dc.subjectquorum sensingen
dc.subjectcooperationen
dc.subjectvirulenceen
dc.titleSecreted virulence factors: evolution, ecology and therapeutic manipulationen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen
dc.rights.embargodate2100-12-31
dcterms.accessRightsRestricted Accessen


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