| Summary: | <p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia </it>are opportunistic Gram-negative bacteria that can cause chronic pulmonary infections in patients with cystic fibrosis. These bacteria demonstrate a high-level of intrinsic antibiotic resistance to most clinically useful antibiotics complicating treatment. We previously identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND) efflux pumps in the genome of <it>B. cenocepacia </it>J2315, but the contribution of these pumps to the intrinsic drug resistance of this bacterium remains unclear.</p> <p>Results</p> <p>To investigate the contribution of efflux pumps to intrinsic drug resistance of <it>B. cenocepacia </it>J2315, we deleted 3 operons encoding the putative RND transporters RND-1, RND-3, and RND-4 containing the genes <it>BCAS0591</it>-<it>BCAS0593</it>, <it>BCAL1674</it>-<it>BCAL1676</it>, and <it>BCAL2822</it>-<it>BCAL2820</it>. Each deletion included the genes encoding the RND transporter itself and those encoding predicted periplasmic proteins and outer membrane pores. In addition, the deletion of <it>rnd-3 </it>also included <it>BCAL1672</it>, encoding a putative TetR regulator. The <it>B. cenocepacia rnd-3 </it>and <it>rnd-4 </it>mutants demonstrated increased sensitivity to inhibitory compounds, suggesting an involvement of these proteins in drug resistance. Moreover, the <it>rnd-3 </it>and <it>rnd-4 </it>mutants demonstrated reduced accumulation of N-acyl homoserine lactones in the growth medium. In contrast, deletion of the <it>rnd-1 </it>operon had no detectable phenotypes under the conditions assayed.</p> <p>Conclusion</p> <p>Two of the three inactivated RND efflux pumps in <it>B. cenocepacia </it>J2315 contribute to the high level of intrinsic resistance of this strain to some antibiotics and other inhibitory compounds. Furthermore, these efflux systems also mediate accumulation in the growth medium of quorum sensing molecules that have been shown to contribute to infection. A systematic study of RND efflux systems in <it>B. cenocepacia </it>is required to provide a full picture of intrinsic antibiotic resistance in this opportunistic bacterium.</p>
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