Etude de la réponse de Brucella melitensis 16M aux molécules signal du Quorum Sensing

  • Julien Lemaire

Student thesis: Doc typesDoctor of Sciences


Quorum Sensing is a bacterial communication system which allows the coordinated gene expression within a population regarding its density and/or environmental properties (diffusion, flow…). In Gram negative bacteria, Quorum Sensing is based on the synthesis of N-acyl-L-homoserine lactones (AHLs) and the detection of these signal molecules by LuxR-type transcriptional regulators. When AHLs concentration reached a threshold (quorum), these molecules bind to the LuxR regulator and lead to conformational changes driving the modification of the regulator activity. Numerous phenomenons are regulated by QS (biofilm formation, fruiting bodies, antibiotics synthesis…), so a competitor able to disturb/inhibit this system could have an advantage on bacteria using Quorum Sensing. The production of inhibitors or enzymes able to degrade signal molecules (AHL-lactonase and acylase) are part of a mechanism called Quorum Quenching. Brucella melitensis, a Gram negative pathogenic bacterium, possesses a Quorum Sensing system constituted by two LuxR-type regulators (called BabR and VjbR) and an AHL identified as a dodecanoyl-homoserine lactone (C12-HSL). While BabR function is unknown, VjbR is involved in the virulence of this pathogen by regulating the expression of two major virulence factors: a flagellum and a type four secretion system. AHLs have a repressor effect on these two structures, and this effect is mediated by VjbR. In order to investigate the role of Quorum Sensing in B. melitensis, global proteomic and transcriptomic studies were performed on wild type, ∆babR and ∆vjbR mutant strains. These studies demonstrate that Quorum Sensing regulates 5% of Brucella genome in the condition tested, confirming that Quorum Sensing is a global regulation system in B. melitensis. Numerous targets of the two regulators are involved in virulence, stress response, metabolism, cell wall structure… suggesting an important role of Quorum Sensing in the achievement of the infectious cycle of B. melitensis. The study of a putative AHL-acylase produced by Brucella demonstrates that this enzyme is an extracellular enzyme able to inactivate AHL signal molecules. Mice infected with an AHL-acylase mutant strain develop a bigger splenomegaly and have a higher bacterial charge in the spleen compared to the wild type strain. These data suggest that Brucella AHL-acylase have also an important role in the infectious cycle of B. melitensis.
Date of Award18 Nov 2009
Original languageFrench
Awarding Institution
  • University of Namur
SupervisorJEAN-JACQUES LETESSON (Supervisor), Xavier De Bolle (President), Jan MICHIELS (Jury), Stephan Kohler (Jury) & Karine Van Doninck (Supervisor)

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