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J. Bacteriol. doi:10.1128/JB.00265-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mutations of the Quorum Sensing-dependent regulator VjbR lead to drastic surface modifications in Brucella melitensis

Sophie Uzureau, Marie Godefroid, Chantal Deschamps, Julien Lemaire, Xavier De Bolle, and Jean-Jacques Letesson*

Unité de Recherche en Biologie Moléculaire, Laboratoire d'Immunologie-Microbiologie, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium

* To whom correspondence should be addressed. Email: jean-jacques.letesson{at}fundp.ac.be.


   Abstract

Successful establishment of infection by bacterial pathogens requires fine-tuning of virulence related genes. Quorum Sensing (QS) is a global regulation process based on the production, detection and response to small diffusible molecules, called N-acyl-homoserine lactone (AHL) in Gram negative bacteria. In numerous species, QS has been shown to regulate genes involved in the establishment of pathogenic interactions with their host.

B. melitensis produces N-dodecanoyl homoserine lactones (C12-HSL), which down regulate the expression of flagellar genes and of the virB operon (encoding a type IV secretion system), both encoding surface virulence factors. A QS-related regulator, called VjbR, was identified as a transcriptional activator of these genes. We hypothesized that VjbR mediates the C12-HSL effects described above. VjbR alleles mutated in the AHL-binding domain were constructed to test this hypothesis. These alleles expressed in trans in a {Delta}vjbR background behave as constitutive regulators both in vitro and in cellular model of infection. Interestingly, these B. melitensis strains, unable to respond to AHLs, spontaneously aggregate in liquid culture. Preliminary characterization of these strains showed an altered expression of some outer membrane proteins (Omps) and an overproduction of a matrix forming exopolysaccharide, suggesting for the first time that B. melitensis could form biofilms. Altogether these results indicate that QS through VjbR is a major regulatory system of important cell surface structures of Brucella and as such is playing a key role in host-pathogen interactions.




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