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dc.contributor.authorAlvarez, Sonsirayen
dc.date.accessioned2018-01-31T11:15:15Z
dc.date.available2018-01-31T11:15:15Z
dc.date.issued2014
dc.identifier.urihttp://hdl.handle.net/1842/26084
dc.description.abstracten
dc.description.abstractAn adequate multiplication rate in vivo is crucial for an infectious agent to cause clinical disease and achieve its transmission to new hosts. Despite their key importance, the nutritional and metabolic determinants of pathogen proliferation within the host remain a neglected area of research in infection biology. In this MSc thesis I have investigated the carbon metabolites used by the bacterial intracellular pathogen Listeria monocytogenes to grow within host cells.en
dc.description.abstractPrevious work in the Vazquez-Boland laboratory demonstrated that, via a specific permease named Hpt, L. monocytogenes steals hexose phosphates from the host cell to fuel its rapid intracellular growth. Albeit more slowly, mutants lacking this permease are still able to replicate intracellularly, indicating that Listeria uses other carbon substrates from the host cell. Evidence suggested that free glucose could be this additional carbon substrate. To test this hypothesis, I sought to obtain a glucose utilisation- deficient mutant by disabling the main transport systems involved in glucose uptake by L. monocytogenes. A double mutant was constructed which lacked the central component of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) Hpr (PtsH) necessary for PTS- dependent sugar transport, plus the main non -PTS specific glucose transporter GIcU1. The double ptsHIglucU1 knockout mutant was virtually unable to grow on glucose in vitro and to proliferate within HeLa epithelial cells in conditions in which free glucose is in excess, indicating that glucose is a main intracellular carbon source for L. monocytogenes.en
dc.description.abstractalso sought to provide evidence for this conclusion from the host cell side. Using siRNA knockdown assays, HeLa cells were depleted of hexokinase, the enzyme that converts all the incoming free glucose into glucose -6- phosphate. A Ahpt mutant unable to use hexose phosphates showed wild -type growth in the hexokinase -depleted host cells, further indicating that free glucose, before conversion into glucose -6- phosphate and entering glycolysis, is a major carbon substrate for intracellular Listeria.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2017 Block 15en
dc.relation.isreferencedbyAlready catalogueden
dc.titleThe role of free glucose as carbon metabolite during intracellular growth of Listeria monocytogenesen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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