Department of Genetic Engineering, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea.
Unit of Antarctic K-Route Expedition, Korea Polar Research Institute, Incheon 21990, South Korea.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10232-10237. doi: 10.1073/pnas.1705437114. Epub 2017 Sep 5.
Bacteria use flagella to move toward nutrients, find its host, or retract from toxic substances. Because bacterial flagellum is one of the ligands that activate the host innate immune system, its synthesis should be tightly regulated during host infection, which is largely unknown. Here, we report that a bacterial leader mRNA from the virulence operon in the intracellular pathogen serovar Typhimurium binds to the coding region of mRNAs in the operon encoding the FljB phase 2 flagellin, a main component of bacterial flagella and the FljA repressor for the FliC phase 1 flagellin, and degrades mRNAs in an RNase E-dependent fashion during infection. A nucleotide substitution of the flagellin gene that prevents the leader RNA-mediated down-regulation increases the -encoded flagellin synthesis, leading to a hypermotile phenotype inside macrophages. Moreover, the nucleotide substitution renders hypervirulent, indicating that FljB-based motility must be compromised in the phagosomal compartment where resides. This suggests that this pathogen promotes pathogenicity by producing a virulence protein and limits locomotion by a -acting leader RNA from the same virulence gene during infection.
细菌利用鞭毛向营养物质移动,寻找宿主,或从有毒物质中缩回。由于细菌鞭毛是激活宿主先天免疫系统的配体之一,因此在宿主感染期间,其合成应该受到严格调控,但这在很大程度上是未知的。在这里,我们报告了一种来自细胞内病原体血清型鼠伤寒沙门氏菌毒力操纵子的细菌前导 mRNA,它与编码 FljB 相 2 鞭毛蛋白的 操纵子中的 mRNAs 的 编码区结合,FljB 相 2 鞭毛蛋白是细菌鞭毛的主要成分,也是 FljA 对 FliC 相 1 鞭毛蛋白的抑制剂,并且在感染过程中以依赖于 RNase E 的方式降解 mRNAs。一种阻止 前导 RNA 介导下调的鞭毛基因核苷酸取代增加了编码的鞭毛蛋白合成,导致巨噬细胞内的超动力表型。此外,该核苷酸取代使 毒力增强,表明在 存在的吞噬体隔间中必须损害 FljB 为基础的运动能力。这表明该病原体通过产生一种毒力蛋白来促进致病性,并在感染期间通过来自同一毒力基因的 前导 RNA 来限制运动。