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Title: The BpeAB-OprB multidrug efflux pump of Burkholderia pseudomallei
Keywords: Burkholderia pseudomallei; antibiotic resistance; efflux pump regulation; quorum sensing; pump inhibitors
Issue Date: 30-Mar-2006
Citation: CHAN YING YING (2006-03-30). The BpeAB-OprB multidrug efflux pump of Burkholderia pseudomallei. ScholarBank@NUS Repository.
Abstract: Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many antimicrobials, including B-lactams, aminoglycosides, macrolides, and polymyxins. The bpeR-bpeA-bpeB-oprB operon encodes a transcriptional repressor, membrane fusion protein, inner membrane protein, and outer membrane protein, respectively, of a multidrug efflux pump of the resistance-nodulation-division family in B. pseudomallei. Comparison of the antimicrobial susceptibility profiles of wild-type B. pseudomallei and its isogenic bpeAB deletion mutant revealed that BpeAB-OprB effluxes the aminoglycosides gentamicin and streptomycin, the macrolide erythromycin. Besides antimicrobial substrates, the expression of bpeAB-oprB was also inducible in the presence of exogenous methylthioadenosine, methylthioribose and spermidine and upon entry into stationary phase. BpeR, a member of the TetR repressor family, functioned as a local regulator of bpeAB-oprB. The expression of bpeR was also induced at stationary phase but lagged behind the induction of bpeAB-oprB expression. Expression of bpeAB-oprB could be advanced to the early exponential phase in the presence of exogenous N-octanoyl- and N-decanoyl-homoserine lactones. Interestingly, BpeAB-OprB was shown to efflux C8-HSL and affected the synthesis of other acyl-homoserine lactones produced by B. pseudomallei. The impact of BpeAB-OprB function on quorum sensing was demonstrated by its effect on optimal production of quorum-sensing-controlled virulence factors such as siderophore and phospholipase C, biofilm formation, and virulence attributes such as cell invasion and cytotoxicity towards human lung epithelial (A549) and human macrophage (THP-1) cells. Both cell invasion and cytotoxicity were significantly attenuated in the bpeAB mutant and bpeR-overexpressing strains, thus suggesting the possibility of attenuating B. pseudomallei virulence using inhibitors of the BpeAB-OprB efflux pump.
Appears in Collections:Ph.D Theses (Open)

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