Virulence associated functions and vaccine potential of the burkholderia mallei type three secretion effector BopA

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Title: Virulence associated functions and vaccine potential of the burkholderia mallei type three secretion effector BopA
Author: Gregory Whitlock
Abstract: The detailed mechanism (s ) of Burkholderia mallei pathogenesis is virtually unknown , with the production of a polysaccharide capsule and presence of secretion systems as the only known mechanisms associated with virulence . Various gram -negative pathogens utilize a secretion system known as type III , which is used to deliver bacterial (effector ) proteins into host cells to modulate immunological and cellular responses . The intracellular survival of B . mallei within murine macrophage J774 .2 cells requires the type III secretion system (TTSS ) , although the effector protein (s ) involved are unknown . Additionally , previous reports have documented that B . mallei TTSS is required for phagosomal membrane lysis and bacterial escape into the macrophage cytoplasm . While progress has been made in demonstrating the importance of the TTSS contribution to B . mallei pathogenicity , additional work is needed to identify the potential secreted (effector ) molecule (s ) involved . BopA , a predicted effector protein of B . mallei , shares 24 % amino acid homology to the TTS effector IcsB of Shigella flexneri , which is responsible for intercellular spread and host cell invasion . Characterization of the involvement of this putative TTS protein with bacterial survival strategies will provide crucial information for the development and assessment of a candidate vaccine . The work presented herein identified an N -terminal portion of BopA sufficient to drive secretion throughout a TTS apparatus and characterized the potential virulence -associated functions of B . mallei TTS protein BopA to subvert the host cell and promote intracellular replication and survival utilizing an in vitro respiratory cell model . Furthermore , in vivo studies assessed the attenuation of virulence offered by the B . mallei bopA mutant . Additionally , evaluation of the immune effectors involved in the protective host response to B . mallei infection identified key cellular and humoral components . Finally , a recombinant BopA sub -unit vaccine was utilized to assess the efficacy as a potential vaccine candidate .
URI: http : / /hdl .handle .net /2152 .3 /210
Date: 2008-08-15

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Virulence associated functions and vaccine potential of the burkholderia mallei type three secretion effector BopA. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /210 .

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