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Concerning Brucella LPS: genetic analysis and role in host- agent interactionTurse, Joshua Edward 30 October 2006 (has links)
B rucella lipopolysaccharide is an important component of virulence in
brucellosis. Recent research in macrophage models has shown that Brucella
LPS does not behave like classical LPS by stimulating potent inflammatory
responses. The central hypothesis of this work is that O-antigen is dynamic
signaling molecular and participates in complex interactions with the host to
promote productive infection. A corollary to this is that the host environment is
dynamic, and Brucella has evolved mechanisms to cope with changing
environments. In an effort to understand the contribution of Brucella LPS to
virulence and pathogenesis, the function of a metabolic locus important in the
synthesis of LPS has been demonstrated and complemented. The spontaneous
loss of LPS expression has been characterized. Contribution of LPS to
acquisition of the host environment in tissue culture and mouse models has
been explored. This work demonstrated that genes outside the O-antigen
biosynthesis ( manBA) cluster contribute to LPS biosynthesis. Further high frequency mutation involving manBA is partly responsible for observed
dissociation of Brucella strains. Finally, work herein attempts to look at the role
of LPS in acquisition of the host environment and shows that LPS is important
for recruiting particular cell populations within a host model of brucellosis.
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