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Title: Intracellular distribution and infection dynamics of virulent and attenuated Salmonella enterica serovar Typhimurium strains in vivo
Author: Foster, G. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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I have demonstrated that the net growth rate of the virulent S. enterica serovar Typhimurium C5 strain can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. The growth acceleration is dependent upon the release of the immunosuppressive cytokine IL-10. This work illustrates that IL-10 production in response to S. enterica requires TLR4 and occurs via signalling pathways involving both TRIF and MyD88 adaptor molecules. Acceleration of the growth of C5 Salmonella does not require simultaneous co-injection of the attenuated bacteria. This indicates that intravenous administration of an S. enterica vaccine strain could potentially exacerbate an established infection with wild-type bacteria. These data could also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain. Secondly, the bacterial distribution of Salmonella enterica within host cells was investigated to try to understand the role of host and bacterial mechanisms in determining bacterial load per host cell. During infections of hosts lacking components of the innate immune system it was found that the bacteria had an increased net growth rate and increased numbers of bacteria per cell; this is in qualitative agreement with the current model of Salmonella in vivo distribution. Temperature sensitive SPI-1 and SPI-2 Salmonella mutants were used to examine the role of bacterial effectors and division in determining bacterial distribution within host cells. This thesis shows that temperature sensitive Salmonella that are unable to replicate at host body temperature reach lower bacterial numbers per host cell. The SPI-2 mutant exhibited a surprising distribution within the host, reaching very high bacterial loads in non-nucleated micro colonies. SPI-2 effectors may promote host cell lysis in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available