<br>PvrA 是一种新型调节剂，通过控制细菌对长链脂肪酸的利用来促进铜绿假单胞菌的发病机制。,Nucleic Acids Research

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PvrA 是一种新型调节剂，通过控制细菌对长链脂肪酸的利用来促进铜绿假单胞菌的发病机制。
Nucleic Acids Research ( IF 13.1 ) Pub Date : 2020-05-14 , DOI: 10.1093/nar/gkaa377
Xiaolei Pan , Zheng Fan , Lei Chen , Chang Liu , Fang Bai , Yu Wei , Zhenyang Tian , Yuanyuan Dong , Jing Shi , Hao Chen , Yongxin Jin , Zhihui Cheng , Shouguang Jin , Jianping Lin , Weihui Wu

在感染宿主期间，铜绿假单胞菌协调全局基因表达以适应宿主环境并抵抗免疫攻击。铜绿假单胞菌含有数百个调节基因，这些基因在控制基因表达方面发挥着重要作用。然而，它们对细菌发病机制的贡献仍然很大程度上未知。在这项研究中，我们分析了从受感染小鼠肺部分离的铜绿假单胞菌细胞的转录组谱，并检查了上调的调控基因在细菌毒力中的作用。新型调节基因pvrA (PA2957) 的突变减弱了急性肺炎模型中的细菌毒力。染色质免疫沉淀 (ChIP)-Seq 和遗传分析表明，PvrA 直接调节参与磷脂酰胆碱利用和脂肪酸分解代谢的基因。当磷脂酰胆碱或棕榈酸用作唯一碳源时， pvrA的突变导致细菌生长缺陷。我们进一步证明棕榈酰辅酶 A 是 PvrA 的配体，增强 PvrA 与其靶启动子的结合亲和力。发现 136 位的精氨酸残基对于 PvrA 结合棕榈酰辅酶 A 至关重要。总体而言，我们的结果揭示了一种新的调控途径，该途径控制参与磷脂酰胆碱和脂肪酸利用的基因，并有助于细菌毒力。

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PvrA is a novel regulator that contributes to Pseudomonas aeruginosa pathogenesis by controlling bacterial utilization of long chain fatty acids.

During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.

更新日期：2020-05-14

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