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Title: Dynamics of Shigella intracellular replication and plasmid maintenance
Author: Martyn, Jessica E.
ISNI:       0000 0004 7654 2818
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Shigella spp. are human specific bacterial pathogens that are an important cause of diarrhoeal disease worldwide. Shigella flexneri can invade into epithelial cells, and survive within the intracellular compartment. Escape from the vacuole and replication in the host cell cytosol are critical for S. flexneri virulence. However, little is known about the basis of bacterial replication inside host cells. There are significant limitations with current methods to study intracellular replication, so fluorescence dilution, which has been developed for studying intracellular salmonellosis was applied to understand the dynamics of S. flexneri survival at a single cell level. Limitations of fluorescence dilution became apparent when it was used to examine interactions of bacteria with non-phagocytic cells. All species of Shigella express a Type III secretion system (T3SS) which is essential for virulence and encoded on a pathogenicity island (PAI). The T3SS PAI is located on a large > 210 kb virulence plasmid, pINV, which is present as single copy in the bacterium. S. flexneri loses pINV during growth in the laboratory, but the mechanisms governing its maintenance are largely unaffected by environmental conditions except the ambient temperature. Shigella sonnei is increasingly becoming an emerging pathogen, which loses pINV at a higher rate than S. flexneri. Toxin-antitoxin systems on S. flexneri and S. sonnei contribute to the vertical transmission of pINV in Shigella populations by mediating post-segregational killing (PSK). Single nucleotide polymorphisms in the Toxin-Antitoxin (TA) system, VapBC, from S. sonnei and S. flexneri have a profound effect on plasmid retention. Additionally, I demonstrated that the genetic background influences the ability of TA systems to mediate PSK and therefore plasmid maintenance. This is due to the different profiles of the target of VapC, tRNAfMet, in Shigella spp. and E. coli. Subtle differences in plasmid maintenance systems and the targets of TA systems can have profound effects on plasmid biology.
Supervisor: Tang, Christoph Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Shigella