School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China.
Cell Rep. 2024 May 28;43(5):114223. doi: 10.1016/j.celrep.2024.114223. Epub 2024 May 14.
Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.
群体感应(QS)是一种由小的可扩散信号分子介导的细胞间通讯机制。先前的研究表明,RpfR 作为顺式-2-十二烯酸(BDSF)QS 信号受体控制伯克霍尔德氏菌中cepacia 的毒力。在这里,我们报告说,脂肪酸酰基辅酶 A 连接酶 DsfR(BCAM2136),它分别有效地催化从月桂酸和油酸体外合成月桂酰辅酶 A 和油酰辅酶 A,作为一个全局转录调节剂通过感知 BDSF 来控制 B. cenocepacia 的毒力。我们表明 BDSF 与 DsfR 具有高亲和力结合,并增强 DsfR 与靶基因启动子 DNA 区域的结合。此外,我们证明了 B. lata 中的 DsfR 同源物 RS02960 结合到靶基因启动子上,并且 BDSF 的感知增强了 RS02960 的结合活性。总之,这些结果深入了解了 DsfR 作为 QS 信号响应调节剂控制细菌毒力的进化异常功能。