Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition.
Global Transcriptional Response of Methylorubrum extorquens to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition.
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DOI：
10.3390/microorganisms9020347
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发表时间：
2021-02-10
期刊：
影响因子：
4.5
通讯作者：
Marx CJ
中科院分区：
文献类型：
--
作者：
Bazurto JV;Riazi S;D'Alton S;Deatherage DE;Bruger EL;Barrick JE;Marx CJ
甲醛对生物分子的反应性的效力和不加选择的性质使其成为普遍的应激源。然而，一些生物如扭脱甲基红菌具有快速有效地减轻甲醛引起的损害的手段。EfgA是最近鉴定的甲醛传感器，预测其响应于升高的甲醛而停止翻译，作为保护细胞的手段。在此，我们研究生长和基因表达的变化，以了解M。扭脱醌对甲醛的反应与EfgA-甲醛介导的翻译反应，以及这种机制如何与甲醛介导的翻译抑制相比。这些不同的翻译抑制机制具有显着的差异：它们各自涉及不同的特定参与者，此外，甲醛还充当一般的多靶点应激源和潜在的碳源。我们目前的研究结果表明，除了其特征的影响翻译，功能EfgA允许一个快速和强大的转录反应，甲醛和EfgA的去除导致升高的蛋白质毒性和遗传毒性的压力在甲醛水平增加的存在下。我们还发现，EfgA-甲醛-和卡那霉素介导的翻译抑制共享许多翻译抑制的下游后果。我们的工作揭示了功能性EfgA在经历甲醛胁迫后制定的额外的调控层，并进一步证明了该蛋白在该模型甲基营养菌中在转录和翻译水平上的重要性。
The potency and indiscriminate nature of formaldehyde reactivity upon biological molecules make it a universal stressor. However, some organisms such as Methylorubrum extorquens possess means to rapidly and effectively mitigate formaldehyde-induced damage. EfgA is a recently identified formaldehyde sensor predicted to halt translation in response to elevated formaldehyde as a means to protect cells. Herein, we investigate growth and changes in gene expression to understand how M. extorquens responds to formaldehyde with and without the EfgA-formaldehyde-mediated translational response, and how this mechanism compares to antibiotic-mediated translation inhibition. These distinct mechanisms of translation inhibition have notable differences: they each involve different specific players and in addition, formaldehyde also acts as a general, multi-target stressor and a potential carbon source. We present findings demonstrating that in addition to its characterized impact on translation, functional EfgA allows for a rapid and robust transcriptional response to formaldehyde and that removal of EfgA leads to heightened proteotoxic and genotoxic stress in the presence of increased formaldehyde levels. We also found that many downstream consequences of translation inhibition were shared by EfgA-formaldehyde- and kanamycin-mediated translation inhibition. Our work uncovered additional layers of regulatory control enacted by functional EfgA upon experiencing formaldehyde stress, and further demonstrated the importance this protein plays at both transcriptional and translational levels in this model methylotroph.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
开发针对甲甲基甲虫的优化培养基，菌株和高通量培养方法。
影响因子：
3.7
作者：
Delaney NF;Kaczmarek ME;Ward LM;Swanson PK;Lee MC;Marx CJ
通讯作者：
Marx CJ
影响因子：
16
作者：
Kohanski MA;DePristo MA;Collins JJ
通讯作者：
Collins JJ
影响因子：
2.6
作者：
Ireland, HE;Harding, SJ;Williams, JHH
通讯作者：
Williams, JHH
影响因子：
11
作者：
Höög, JO;Hedberg, JJ;Svensson, S
通讯作者：
Svensson, S