Oxidative stress activates transcription of Salmonella pathogenicity island-2 genes in macrophages.
Oxidative stress activates transcription of Salmonella pathogenicity island-2 genes in macrophages.
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DOI：
10.1016/j.jbc.2022.102130
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发表时间：
2022-07
影响因子：
4.8
通讯作者：
Vazquez-Torres, Andres
中科院分区：
文献类型：
--
作者：
Kim, Ju-Sim;Liu, Lin;Davenport, Bennett;Kant, Sashi;Morrison, Thomas E.;Vazquez-Torres, Andres
沙门氏菌致病性岛-2 （SPI-2）基因簇编码的III型分泌系统通过干扰含沙门氏菌液泡沿降解途径的成熟，促进非伤寒沙门氏菌的细胞内生长。SPI-2基因产物还能保护沙门氏菌免受吞噬细胞NADPH氧化酶2 （NOX2）合成的活性氧（ROS）的抗菌活性。然而，炎症ROS与细胞内沙门氏菌激活SPI-2基因转录之间的潜在关系尚不清楚。在这里，我们发现在先天宿主反应中产生的ROS刺激了SPI-2基因的转录。我们发现SPI-2基因在沙门氏菌维持氧化应激条件下的表达涉及DksA，这是一种已知的调节细菌对营养应激的严格反应的蛋白质。我们还证明，DnaJ的J和锌-2氧化还原酶结构域以及DnaK伴侣的atp酶活性有助于DksA装载到带有SPI-2启动子的RNA聚合酶上。此外，在经历氧化应激的沙门氏菌中，dksa驱动的SPI-2基因转录取决于上游的OmpR、PhoP和SsrB信号事件，这些信号事件参与了类核蛋白的去除，同时将RNA聚合酶募集到SPI-2启动子区域。综上所述，我们的研究结果表明，在受到巨噬细胞呼吸爆发产生的ROS的沙门氏菌中，SPI-2基因转录的激活可以保护这种细胞内病原体免受nox2介导的杀伤。我们认为沙门氏菌已选择炎性ROS诱导spi -2介导的针对NOX2宿主防御的保护性反应。
The type III secretion system encoded in the Salmonella pathogenicity island-2 (SPI-2) gene cluster facilitates intracellular growth of nontyphoidal Salmonella by interfering with the maturation of Salmonella-containing vacuoles along the degradative pathway. SPI-2 gene products also protect Salmonella against the antimicrobial activity of reactive oxygen species (ROS) synthesized by the phagocyte NADPH oxidase 2 (NOX2). However, a potential relationship between inflammatory ROS and the activation of transcription of SPI-2 genes by intracellular Salmonella is unclear. Here, we show that ROS engendered in the innate host response stimulate SPI-2 gene transcription. We found that the expression of SPI-2 genes in Salmonella-sustaining oxidative stress conditions involves DksA, a protein otherwise known to regulate the stringent response of bacteria to nutritional stress. We also demonstrate that the J and zinc-2-oxidoreductase domains of DnaJ as well as the ATPase activity of the DnaK chaperone facilitate loading of DksA onto RNA polymerase complexed with SPI-2 promoters. Furthermore, the DksA-driven transcription of SPI-2 genes in Salmonella experiencing oxidative stress is contingent on upstream OmpR, PhoP, and SsrB signaling events that participate in the removal of nucleoid proteins while simultaneously recruiting RNA polymerase to SPI-2 promoter regions. Taken together, our results suggest the activation of SPI-2 gene transcription in Salmonella subjected to ROS produced by the respiratory burst of macrophages protects this intracellular pathogen against NOX2-mediated killing. We propose that Salmonella have co-opted inflammatory ROS to induce SPI-2-mediated protective responses against NOX2 host defenses.
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影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
影响因子：
4.2
作者：
Osborne SE;Coombes BK
通讯作者：
Coombes BK
影响因子：
4.8
作者：
Henard, Calvin A.;Bourret, Travis J.;Vazquez-Torres, Andres
通讯作者：
Vazquez-Torres, Andres
DOI：
10.1073/pnas.0505401102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Coombes, BK;Wickham, ME;Finlay, BB
通讯作者：
Finlay, BB
影响因子：
3.6
作者：
Henard CA;Tapscott T;Crawford MA;Husain M;Doulias PT;Porwollik S;Liu L;McClelland M;Ischiropoulos H;Vázquez-Torres A
通讯作者：
Vázquez-Torres A