O'Connor Kathleen, Fletcher Susanne A, Csonka Laszlo N
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17522-7. doi: 10.1073/pnas.0906160106. Epub 2009 Oct 1.
Mg(2+) homeostasis is important for Salmonella pathogenesis. In Salmonella enterica, the transcription of the mgtA gene, which encodes a Mg(2+) transporter, is regulated by a Mg(2+)-sensing riboswitch [Cromie MJ, Shi Y, Latifi T, Groisman EA (2006) Cell 125:71-84]. In a genetic analysis of the determinants of thermotolerance in S. enterica serovar Typhimurium, we isolated the chr-1 mutation that increased the resistance of exponential phase cells to killing by high temperature. This mutation is a single base change in the mgtA riboswitch that causes high-level constitutive expression of mgtA. We showed that another mgtA riboswitch mutation, DeltaUTR(re-100), which had been constructed by Cromie et al., also confers similar increased thermotolerance. Surprisingly, the chr-1 mutation is located at a position that would not be predicted to be important for the regulatory function of the riboswitch. We obtained physiological evidence suggesting that the chr-1 mutation increases the cytosolic free Mg(2+) concentration. High-level expression of the heterologous MgtE Mg(2+) transport protein of Bacillus subtilis also enhanced the thermotolerance of S. enterica. We hypothesize that increased Mg(2+) accumulation might enhance thermotolerance by protecting the integrity of proteins or membranes, by mitigating oxidative damage or acting as an inducer of thermoprotective functions.
镁离子稳态对沙门氏菌致病机制很重要。在肠炎沙门氏菌中,编码镁离子转运蛋白的mgtA基因的转录受一种镁离子感应核糖开关调控[克罗米·M·J、施·Y、拉蒂菲·T、格罗伊斯曼·E·A(2006年)《细胞》125卷:71 - 84页]。在对肠炎沙门氏菌鼠伤寒血清型耐热性决定因素的遗传分析中,我们分离出chr - 1突变,该突变增加了对数生长期细胞对高温杀伤的抗性。此突变是mgtA核糖开关中的单个碱基变化,导致mgtA高水平组成型表达。我们表明,克罗米等人构建的另一个mgtA核糖开关突变DeltaUTR(re - 100)也赋予类似的耐热性增加。令人惊讶的是,chr - 1突变位于一个预计对核糖开关调控功能不重要的位置。我们获得了生理证据,表明chr - 1突变增加了胞质游离镁离子浓度。枯草芽孢杆菌异源MgtE镁离子转运蛋白的高水平表达也增强了肠炎沙门氏菌的耐热性。我们推测,镁离子积累增加可能通过保护蛋白质或膜的完整性、减轻氧化损伤或作为热保护功能的诱导剂来增强耐热性。