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Title: The characterization of the lipoprotein VacJ in Burkholderia pseudomallei and Burkholderia thailandensis
Author: Lim, J.
ISNI:       0000 0004 5364 2744
Awarding Body: London School of Hygiene and Tropical Medicine (University of London)
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2014
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Burkholderia pseudomallei, the causative agent of melioidosis, has evolved multiple strategies to facilitate survival in the environment and can cause serious disease in the human host. The lipoprotein BPSL3147 (VacJ) was previously shown to be important in the growth and survival of B. pseudomallei in an in vivo mouse model and a VacJ transposon mutant was highly attenuated. This work has focused on elucidating the role of VacJ as a virulence determinant in B. pseudomallei. The gene was characterized using bioinformatic and genetic techniques, utilizing comparisons with B. thailandensis to study the in vivo and in vitro roles. In this study a rationally defined B. pseudomallei VacJ deletion mutant was constructed, verified and evaluated. The VacJ mutant was able to colonize mice organs during the initial infection phase, but was unable to sustain the infection. In in vitro assays the VacJ mutant did not display any defect in early steps of the intracellular lifecycle. However, VacJ appears to play a contributory role to human serum resistance, as evidenced by the serum susceptibility of an acapsular B. pseudomallei ΔBPSL3147 mutant and B. thailandensis VacJ mutants. Taken together, VacJ contributes to virulence by affecting the outer membrane of B. pseudomallei and B. thailandensis affecting serum resistance sensitivity. The B. pseudomallei VacJ mutant was also investigated for potential as a live attenuated vaccine and displayed partial protection against a lethal challenge in an acute intranasal mice infection model.
Supervisor: Wren, B. W. Sponsor: DSO National Laboratories, Singapore
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral