<it>Brucella melitensis </it>VjbR and C₁₂-HSL regulons: contributions of the <it>N</it>-dodecanoyl homoserine lactone signaling molecule and LuxR homologue VjbR to gene expression

<p>Abstract</p> <p>Background</p> <p>Quorum sensing is a communication system that regulates gene expression in response to population density and often regulates virulence determinants. Deletion of the <it>luxR </it>homologue <it>vjbR </it>highly attenuates intracellular survival of <it>Brucella melitensis </it>and has been interpreted to be an indication of a role for QS in <it>Brucella </it>infection. Confirmation for such a role was suggested, but not confirmed, by the demonstrated <it>in vitro </it>synthesis of an auto-inducer (AI) by <it>Brucella </it>cultures. In an effort to further delineate the role of VjbR to virulence and survival, gene expression under the control of VjbR and AI was characterized using microarray analysis.</p> <p>Results</p> <p>Analyses of wildtype <it>B. melitensis </it>and isogenic Δ<it>vjbR </it>transciptomes, grown in the presence and absence of exogenous <it>N</it>-dodecanoyl homoserine lactone (C₁₂-HSL), revealed a temporal pattern of gene regulation with variances detected at exponential and stationary growth phases. Comparison of VjbR and C₁₂-HSL transcriptomes indicated the shared regulation of 127 genes with all but 3 genes inversely regulated, suggesting that C₁₂-HSL functions via VjbR in this case to reverse gene expression at these loci. Additional analysis using a Δ<it>vjbR </it>mutant revealed that AHL also altered gene expression in the absence of VjbR, up-regulating expression of 48 genes and a <it>luxR </it>homologue <it>blxR </it>93-fold at stationary growth phase. Gene expression alterations include previously un-described adhesins, proteases, antibiotic and toxin resistance genes, stress survival aids, transporters, membrane biogenesis genes, amino acid metabolism and transport, transcriptional regulators, energy production genes, and the previously reported <it>fliF </it>and <it>virB </it>operons.</p> <p>Conclusions</p> <p>VjbR and C₁₂-HSL regulate expression of a large and diverse number of genes. Many genes identified as virulence factors in other bacterial pathogens were found to be differently expressed, suggesting an important contribution to intracellular survival of <it>Brucella</it>. From these data, we conclude that VjbR and C₁₂-HSL contribute to virulence and survival by regulating expression of virulence mechanisms and thus controlling the ability of the bacteria to survive within the host cell. A likely scenario occurs via QS, however, operation of such a mechanism remains to be demonstrated.</p>