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dc.contributor.advisorO'Byrne, Conor
dc.contributor.advisorKaratzas, Kimon-Andreas
dc.contributor.authorFeehily, Conor
dc.date.accessioned2014-10-09T08:21:45Z
dc.date.available2014-10-09T08:21:45Z
dc.date.issued2014-07-22
dc.identifier.urihttp://hdl.handle.net/10379/4628
dc.description.abstractThe foodborne pathogen Listeria monocytogenes is the causative agent of listeriosis in humans and other animals. This disease can have a fatality rate of up to 30% in infected patients and leads to spontaneous abortion in pregnant women. The most common source of the bacteria is from contaminated food stuffs that are either consumed raw or are minimally processed. The bacterium has evolved several mechanisms to ensure survival in sometimes harsh environments such as acidified foods and the low pH of the stomach. Among these mechanisms is the glutamate decarboxylase (GAD) system. This is widely considered to allow the bacteria to maintain a favourable intracellular pH in conditions where the extracellular pH has dropped. The GAD system involves the import of extracellular glutamate coupled to the export of gamma-aminobutyric acid (GABA). Inside the cell, the glutamate is converted to GABA by GAD which consumes intracellular protons. GABA can then leave the cell in exchange for further glutamate molecules. The glutamate/GABA antiport is carried out by GadT, a membrane protein. Our work shows that the GAD system has undergone divergent evolution between closely related strains of L. monocytogenes. There is a split between the action of extracellular GAD activity (GADe) and intracellular GAD activity (GADi) in strains 10403S and EGD-e. We demonstrate that among the 3 genes encoding for decarboxylase enzymes, gadD2, is closely associated with GADe while gadD3 is central to GADi. Overall the regulation of the GAD system does not appear to occur at a transcriptional level in stationary phase cells. Furthermore, we present the first evidence of the GABA shunt pathway in L. monocytogenes. This pathway has the potential to metabolise GABA produced by the cell and we identify a link between this pathway and acid resistance. A murine model of study has shown that deletion of up to two GAD genes reduces bacterial load in the spleen and liver indicating a redundancy in the GAD system in L. monocytogenes and a potential role in virulence.en_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectGAD systemen_US
dc.subjectListeria monocytogenesen_US
dc.subjectMicrobial metabolismen_US
dc.subjectMicrobiologyen_US
dc.subjectStress responseen_US
dc.subjectScienceen_US
dc.titleElucidation of the role of the glutamate decarboxylase system and the gamma-aminobutyric acid shunt pathway in the stress response of Listeria monocytogenesen_US
dc.typeThesisen_US
dc.contributor.funderScience Foundation Irelanden_US
dc.local.noteA mechanism by which the foodborne pathogen Listeria monocytogenes survives passage through the acidic stomach was studied. The study highlighted the importance of this mechanism in the virulence of the bacteria and also identified a new metabolic pathway associated with acid survival.en_US
dc.local.finalYesen_US
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland