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Title: Listeria monocytogenes : understanding the interaction of pathogen and host physiology during intracellular growth
Author: Shahraz, Mohammed
ISNI:       0000 0004 2737 5400
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2013
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Listeria monocytogenes (L. monocytogenes) are Gram-positive, facultatively anaerobic and intracellular bacilli, occupying a wide range of ecological niches and are responsible for a number of serious infections in man. Primarily transmitted to humans through contaminated food stocks, L. monocytogenes invade mammalian cells in a phagosome, escaping and growing in the cell cytoplasm. Currently, there is a great deal of information about pathogenesis of L. monocytogenes, however, much less is known about the physiology of the bacteria. In particular, very little is known about the physiology during intracellular growth and even less about host cell physiology and changes in response to infection. The focus of this research was to address these issues using a multidisciplinary approach, utilising multiple biological techniques. The catabolic metabolism of L.monocytogenes was elucidated using mutagenesis and protein purification studies. The results are not completely conclusive; however, it was shown that unlike in Escherichia coli, L.moncytogenes may not be dependent on fermentation enzymes Ldh and Pflb during anaerobic growth. Instead anaerobic respiration is hypothesised, utilising a putative fumarate reductase with fumarate as a terminal electron acceptor. The putative fumarate reductase gene was purified and confirmed to have enzymatic activity.External and internal metabolism of HeLa cells, and the effect of L.monocytogenes infection was elucidated by mass spectrometry. The external metabolomic studies proved inconclusive. The internal metabolomic studies show that a number of key amino acids are being sequestered by L.monocytogenes during the course of an infection. Also, the studies show that a large number of carbon compounds are being sequestered by L.monocytogenes, pointing to a complex carbon metabolism for L.monocytogenes during intracellular growth. A targeted analysis of the nitrogen metabolism of L.monocytogenes has shown that L.monocytogenes may utilise a number of nitrogen compounds with glutamine and glutamate being particularly important. The ability to synthesise glutamine de novo is shown to be essential for normal intracellular growth.
Supervisor: Goodacre, Roy; Roberts, Ian; Westerhoff, Hans Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Listeria monocytogenes ; Intracellular parasite ; Metabolism