Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion.
Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion.
复制标题
新型调节剂LoiA介导的低氧张力诱导鼠伤寒沙门氏菌侵袭的信号转导通路
DOI：
10.1371/journal.ppat.1006429
复制
发表时间：
2017-06
期刊：
影响因子：
6.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Jiang L;Feng L;Yang B;Zhang W;Wang P;Jiang X;Wang L
鼠伤寒沙门氏菌（S.鼠伤寒沙门氏菌（Typhimurium）是人和动物的主要肠道病原体。沙门氏菌致病岛1（SPI-1）编码的毒力基因是沙门氏菌所必需的。鼠伤寒入侵。虽然氧（O2）限制是宿主条件下SPI-1诱导的重要信号，但该信号如何被接收并整合到S.鼠伤寒沙门氏菌不明确。在这里，我们报告了一个信号转导途径，激活SPI-1的表达，响应低O2。SPI-14（STM14_1008）中编码的一种新的调节因子，称为LoiA（低氧诱导因子A），直接与启动子结合并激活hilD的转录，导致hilA（SPI-1的主激活因子）的激活。在低O2条件下，loiA的缺失显著降低了hilA、hilD和其他代表性SPI-1基因（sipB、spaO、invH、prgH和invF）的转录。LoiA对低O2信号的响应由ArcB/ArcA双组分系统介导。arcA或arcB的缺失显着降低loiA在低O2条件下的转录。我们还证实了SPI-14对S.通过影响入侵而影响鼠伤寒沙门氏菌毒力，并且loiA是SPI-14的毒力决定因子。小鼠感染试验表明，S.鼠伤寒沙门氏菌的毒力被严重衰减的删除后，整个SPI-14区域或单个loiA基因的口服感染，而毒力不受任何删除后腹腔感染。所描述的信号转导途径代表了S.鼠伤寒沙门氏菌感知和响应宿主肠道的低氧条件以进行入侵。SPI-14编码的loiA是该途径的重要元件，其将低O2信号整合到SPI-1调节系统中。因此，获得SPI-14对于S.作为肠道病原体的鼠伤寒。
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intestinal pathogen of both humans and animals. Salmonella pathogenicity island 1 (SPI-1)-encoded virulence genes are required for S. Typhimurium invasion. While oxygen (O2) limitation is an important signal for SPI-1 induction under host conditions, how the signal is received and integrated to the central SPI-1 regulatory system in S. Typhimurium is not clear. Here, we report a signal transduction pathway that activates SPI-1 expression in response to low O2. A novel regulator encoded within SPI-14 (STM14_1008), named LoiA (low oxygen induced factor A), directly binds to the promoter and activates transcription of hilD, leading to the activation of hilA (the master activator of SPI-1). Deletion of loiA significantly decreased the transcription of hilA, hilD and other representative SPI-1 genes (sipB, spaO, invH, prgH and invF) under low O2 conditions. The response of LoiA to the low O2 signal is mediated by the ArcB/ArcA two-component system. Deletion of either arcA or arcB significantly decreased transcription of loiA under low O2 conditions. We also confirmed that SPI-14 contributes to S. Typhimurium virulence by affecting invasion, and that loiA is the virulence determinant of SPI-14. Mice infection assays showed that S. Typhimurium virulence was severely attenuated by deletion of either the entire SPI-14 region or the single loiA gene after oral infection, while the virulence was not affected by either deletion after intraperitoneal infection. The signal transduction pathway described represents an important mechanism for S. Typhimurium to sense and respond to low O2 conditions of the host intestinal tract for invasion. SPI-14-encoded loiA is an essential element of this pathway that integrates the low O2 signal into the SPI-1 regulatory system. Acquisition of SPI-14 is therefore crucial for the evolution of S. Typhimurium as an intestinal pathogen.