Contribution à l'étude du système BAC "Biofilm Associated Cluster" chez Pseudomanas aeruginosa.

Abstract : Pseudomonas aeruginosa (PA) is a Gram-negative bacterium, opportunistic pathogen, involved in a large number of nosocomial infections. This microorganism is also the main infectious agent involved in bronchopulmonary infections in cystic fibrosis patients. This pre-eminence is partly due to the ability of PA to form biofilms, which confers to the bacterial cells an increased resistance to antibiotics. In our laboratory, a differential proteomic analysis allowed to demonstrate in 2004, the existence of a specific proteome when the bacterium grows in the biofilm mode. This study allowed identifying about 40 proteins, specifically accumulated when bacteria adhere to a surface. Among these proteins, the hypothetical protein PA3731 has been particularly investigated. This protein is involved in the biofilm formation, the rhamnolipids production, the resistance to tobramycin and the swarming mobility. Bioinformatic research showed that the pA3731 gene belongs to a cluster of 4 genes ranging from pA3729 to pA3732 (BAC system), which could be involved in the development and / or regulation of the same protein system. This hypothesis was the starting point of this thesis work. The present study confirmed the involvement of the BAC system in the biofilm formation, the antibiotic resistance and the rhamnolipid production in PA. Proteomic studies highlighted the implication of this system in the expression of the MexEF-OprN pump and that of the OprD porin, and in the regulation of Quorum Sensing. Interactomic investigations, conducted in parallel, showed a strong interaction between PA3731 and PA3732 proteins. These studies have also pointed out a strong interaction between these proteins and rhamnolipids. All these results suggest that the BAC system could play a major role in the transfer of rhamnolipids to the extracellular environment.
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Brahim Saffiedine. Contribution à l'étude du système BAC "Biofilm Associated Cluster" chez Pseudomanas aeruginosa.. Chimie thérapeutique. Normandie Université, 2019. Français. ⟨NNT : 2019NORMR018⟩. ⟨tel-02272748⟩

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