Brucella melitensis is an intracellular facultative Gram-negative, nonmotile bacterium that causes Brucellosis. The purpose of this work is to investigate the expression of flagellar machinery, and the function of flagellar-like genes recently identified in Brucella melitensis. B. melitensis flagellar gene homologues may encode proteins that form a flagellar type and/or type III secretion system which contributes to host colonization, intracellular survival of Brucella spp. and/or inhibit the host immune system. The major aims of this work are: 1) to generate knockouts of flagellar-related genes, 2) to perform gene complimentation of flagellar-like genes disrupted in B. melitensis, 3) to investigate the extent of infection using flagellar-related gene mutants of B. melitensis, and 4) to perform microarray analysis of the B. melitensis gene expression profile upon host infection focusing on the flagellar-like genes. The proposed studies will provide information on potential pathogenic mechanisms of B. melitensis and related organisms. Knowledge of the effector mechanisms involved in pathogenicity will allow us to develop target specific therapies (e.g. vaccines) and will shed light on potential pathways of immune modulation.
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