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Title: The role of the BipA GTPase in Salmonella enteritidis
Author: White, Angeline
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2001
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The BipA protein is a novel GTPase of the ribosome-binding GTPase superfamily that is highly conserved in eubacterial and plants. Recent studies suggest that it regulates virulence-associated processes in enteropathogenic Escherichia coli, raising the question of whether it has a more general role in the pathogenesis of enteric bacteria. To address this issue, a bipA null mutant of Salmonella enteritidis has been constructed, validated, and characterised in in vitro and in vivo assays. In vitro, the mutant showed no significant growth defects but positively regulated the expression of several surface appendages including SEF14, SEF17 and flagella. Consistent with the flagella results, BipA also increased the cell motility of S. enteritidis. Conversely, BipA was shown to negatively regulate the expression of SEF21 and another fimbrial system, possibly the plasmid encoded fimbriae (PEF). Growth of the mutant in cultured macrophages was assessed using a gentamicin resistance assay, where a decrease in its survival, relative to the parent strain, was observed. Moreover, the mutant had an impaired response to oxidative stress. In vivo studies were used to compare the invasion/colonisation characteristics of the bipA null mutant with those of the wild type parent strain. Using a one day old chick model, only a slight reduction in the number of CFU for the mutant was found in the liver and spleen compared to the wild type strain. However, studies with the mouse model of infection indicated that the bipA mutant is not significantly attenuated relative to the parent strain. Taken together, these results suggest that the BipA GTPase plays a more significant role in survival within the environment than in the host. Analysis of the genes downstream of bipA uncovered a unique 5.8kb region found only in specific Salmonella serovars. This region was found to have a lower GC content, compared to that of the normal Salmonella chromosome, which suggested that it had been acquired by horizontal gene transfer and hence might encoded pathogenicity-related components.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Virulence; Ribosomal binding proteins