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FtcR Is a New Master Regulator of the Flagellar System of Brucella melitensis 16M with Homologs in Rhizobiaceae

Unité de Recherche en Biologie Moléculaire, Laboratoire d'Immunologie-Microbiologie, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium,¹ Centre d'Etude et de Recherches Vétérinaires et Agronomiques, Brussels, Belgium,² Service de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium³

Received 18 May 2006/ Accepted 5 October 2006

The flagellar regulon of Brucella melitensis 16M contains 31 genes clustered in three loci on the small chromosome. These genes encode a polar sheathed flagellum that is transiently expressed during vegetative growth and required for persistent infection in a mouse model. By following the expression of three flagellar genes (fliF, flgE, and fliC, corresponding to the MS ring, hook, and filament monomer, respectively), we identified a new regulator gene, ftcR (flagellar two-component regulator). Inactivation of ftcR led to a decrease in flagellar gene expression and to impaired Brucella virulence. FtcR has a two-component response regulator domain as well a DNA binding domain and is encoded in the first flagellar locus of B. melitensis. Both the ftcR sequence and its genomic context are conserved in other related -proteobacteria. During vegetative growth in rich medium, ftcR expression showed a peak during the early exponential phase that paralleled fliF gene expression. VjbR, a quorum-sensing regulator of the LuxR family, was previously found to control fliF and flgE gene expression. Here, we provide some new elements suggesting that the effect of VjbR on these flagellar genes is mediated by FtcR. We found that ftcR expression is partially under the control of VjbR and that the expression in trans of ftcR in a vjbR mutant restored the production of the hook protein (FlgE). Finally, FtcR binds directly to the upstream region of the fliF gene. Therefore, our data support the role of FtcR as a flagellar master regulator in B. melitensis and perhaps in other related -proteobacteria.

Published ahead of print on 20 October 2006.

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