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

Weeks, Jenni N.; Galindo, Cristi L.; Drake, Kenneth L.; Adams, L. Garry; Garner, Harold R.; Ficht, Thomas A.

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

dc.contributor.author	Weeks, Jenni N.	en
dc.contributor.author	Galindo, Cristi L.	en
dc.contributor.author	Drake, Kenneth L.	en
dc.contributor.author	Adams, L. Garry	en
dc.contributor.author	Garner, Harold R.	en
dc.contributor.author	Ficht, Thomas A.	en
dc.date.accessioned	2012-08-24T11:21:34Z	en
dc.date.available	2012-08-24T11:21:34Z	en
dc.date.issued	2010-06-08	en
dc.date.updated	2012-08-24T11:21:35Z	en
dc.description.abstract	Background Quorum sensing is a communication system that regulates gene expression in response to population density and often regulates virulence determinants. Deletion of the luxR homologue vjbR highly attenuates intracellular survival of Brucella melitensis and has been interpreted to be an indication of a role for QS in Brucella infection. Confirmation for such a role was suggested, but not confirmed, by the demonstrated in vitro synthesis of an auto-inducer (AI) by Brucella 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. Results Analyses of wildtype B. melitensis and isogenic ΔvjbR transciptomes, grown in the presence and absence of exogenous N-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 ΔvjbR mutant revealed that AHL also altered gene expression in the absence of VjbR, up-regulating expression of 48 genes and a luxR homologue blxR 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 fliF and virB operons. Conclusions 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 Brucella. 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.	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	BMC Microbiology. 2010 Jun 08;10(1):167	en
dc.identifier.doi	https://doi.org/10.1186/1471-2180-10-167	en
dc.identifier.uri	http://hdl.handle.net/10919/18838	en
dc.language.iso	en	en
dc.rights	Creative Commons Attribution 4.0 International	en
dc.rights.holder	Jenni N Weeks et al.; licensee BioMed Central Ltd.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.title	Brucella melitensis VjbR and C12-HSL regulons: contributions of the N-dodecanoyl homoserine lactone signaling molecule and LuxR homologue VjbR to gene expression	en
dc.title.serial	BMC Microbiology	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en