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Title: Molecular and functional characterisation of the immunodominant antigens of the obligate intracellular pathogen Lawsonia intracellularis
Author: McAllister, Georgina
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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TlyA deletion mutants in H. pylori and B. hyodysenteriae are attenuated, suggesting that these proteins perform important roles during infection. LsaA (lawsonia surface antigen) the L. intracellularis orthologue, is expressed during infection in vitro and in vivo and suggest that this factor is involved during adherence and/or invasion of intestinal epithelial cells. The principal aim was to characterise function(s) of LsaA. Specifically the putative function as an adhesin was investigated further using a combination of biochemical and molecular approaches (including affinity purification and yeast 2-bybrid) to elucidate possible receptor(s). However, no consistent partner was evident therefore mammalian epithelial cell receptors could not be defined using this range of approaches. It is possible that LsaA’s role in adherence is adventitious – for example, it has been proposed that the TlyA family of proteins possess a regulatory role in bacterial colonisation as opposed to a direct involvement in bacterial adherence. The existence of two conserved putative functional domains S4RNA binding and methyltransferase motifs have been noted in all members of the TlyA family examined to date. These domains are found separately in several protein families known to be involved in gene regulation. Since no system has been developed for mutating genes in L. intracellularis the proteome of a TlyA deletion mutant of H. pylori was compared to its parent to further this potentially new and interesting function of TlyA family proteins. Notably, flagellin B and catalase were absent in the tlyA mutant. Since deletion of tlyA corresponds with changes in expression of several H. pylori genes, it can be concluded that reduced colonisation of H. pylori tlyA mutant is likely to be as a result of effects on expression of virulence genes rather than a direct role in adherence.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available