Burkholderia Pseudomallei: Interaction with Host Cells
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Melioidosis is the serious and often fatal systemic disease of humans and animals resulting from infection from Burkholderia pseudomallei. B. pseudomallei is a Gram-negative bacillus that inhabits the soil and stagnant water of tropical and sub-tropical countries. Infection usually occurs through inhalation or inoculation though ingestion is a common route for animal infections. The disease can occur in almost any organ and symptoms are non-specific leading to common misdiagnosis. B. pseudomallei has increased prevalence for infection in immunocompromised and diabetic patients. Due to the soil dwelling nature of B. pseudomallei this bacteria has a high level of antibiotic resistance. Treatment is often difficult and prolonged, though modern medical treatment has reduced mortality to around 40%. Recent studies have revealed that B. pseudomallei contains numerous virulence mechanisms including bacterial protein secretion systems, lipopolysaccharides, and quorum sensing mechanisms. These systems allow the bacteria to survive and perpetuate especially in host macrophages. It is this interaction and the responses of the host that remain to be elucidated. Many studies have described activation of host signalling pathways or proteins during infection. Often B. pseudomallei mutants are produced to establish the affect these altered bacteria have on the host pathways. This study attempted to examine intact virulence mechanisms by utilising drug and small peptide inhibitors of the host pathways to examine the effect that these have on the invading bacteria. Furthermore, it set out to investigate the processes involved in B. pseudomallei-host interactions. It examined the MAPK, NFAT and NF-B signalling pathways activated in infected macrophages. Further, the resultant chemokine expression and receptor activation on these infected cells was established.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
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immunocompromised and diabetic patients