Identification of genetic loci and transcriptional networks that confer virulence and survival of Brucella melitensis

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Title: Identification of genetic loci and transcriptional networks that confer virulence and survival of Brucella melitensis
Author: Weeks, Jenni Nichole
Abstract: Brucella melitensis is the etiological agent of brucellosis , a zoonotic disease characterized by abortions in ruminant animals and a chronic debilitating disease in humans . Despite genome sequencing , little is known about the genetic elements behind Brucella ?s ability to survive and cause disease . Regulatory networks provide the ability to adapt to changing environments by initiating expression from specific regulons to provide adjustments to metabolism and mechanisms that enhance survival . Little detail is known about transcriptional networks that exist in Brucella , but are of great interest because they could provide information about genetic loci that contribute to virulence and intracellular survival . Transposon mutagenesis identified gene loci that are indispensable for the intracellular replication of B . melitensis , including virulence genes , metabolic defects , and transcriptional regulators . Two transcriptional regulators of interest were identified , MucR and VjbR . VjbR is a LuxR homologue and is associated with the regulation of virulence genes in a density dependent manner in a number of bacterial pathogens , and is consistent with VjbR regulation of virulence genes in B . melitensis . Microarray analysis of ?vjbR and a potential activating signal C12 -HSL revealed that both regulate numerous putative virulence genes , including adhesins , proteases , protein secretion /translocation components , potential effector proteins , lipoproteins , a hemolysin and stress survival aids . This analysis also revealed that C12 -HSL is not an activating signal of VjbR , but instead acts to suppress VjbR activity . MucR is a transcriptional regulator shown to regulate exopolysaccharide synthesis in the closely related Rhizobiales . Microarray analysis of a ?mucR mutant in B . melitensis suggested that MucR contributes to the regulation of nitrogen metabolism and iron sequestering /storage . MucR was also found to regulate genes involved in stress response , regulating several proteases that may contribute to enhanced survival and virulence of the organism . This work identified approximately 1 ,000 genetic loci that may be important to the survival of B . melitensis , revealing potential virulence genes and metabolic defects . Interruption of the VjbR regulon could be a potential chemotherapeutic target for the treatment of brucellosis . Furthermore , this work describes the functions of two gene deletions that are being evaluated as novel attenuated vaccines .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -2970
Date: 2009-05-15

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Identification of genetic loci and transcriptional networks that confer virulence and survival of Brucella melitensis. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -2970 .

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