Distinct Roles of Shewanella oneidensis Thioredoxin in Regulation of Cellular Responses to Hydrogen and Organic Peroxides
Distinct Roles of Shewanella oneidensis Thioredoxin in Regulation of Cellular Responses to Hydrogen and Organic Peroxides
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DOI：
10.1128/aem.01700-19
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发表时间：
2019-11-01
影响因子：
4.4
通讯作者：
Gao, Haichun
中科院分区：
文献类型：
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作者：
Feng, Xue;Sun, Weining;Gao, Haichun
硫氧还蛋白(TRX)和谷氧还蛋白(GRX)抗氧化系统与细菌对氧化应激的反应密切相关，但到目前为止，除了过氧化氢(H_2O_2)外，我们对这些系统在反应活性氧物种(ROS)方面的作用知之甚少。在这项研究中，我们使用环境细菌圆锥希瓦氏菌作为研究模型来研究TRX和GRX在氧化应激反应中的作用，因为它在功能上交织在ROS反应调节因子OxyR和OhrR中。我们发现Trx1是主要的硫醇/二硫化物氧化还原体系，在没有Trx1的情况下，GRX体系在正常情况下是必不可少的。虽然在野生型中Trx1令Trx1黯然失色，但当产量过高时，Trx2在生理上完全可以取代Trx1。Trx1是OxyR发挥阻遏作用所必需的，但更重要的是，它通过调节OhrR而不是OP清除剂OhrA的氧化还原状态，在细胞对有机过氧化物(OP)的反应中发挥关键作用。Trx和grx基因均不依赖于OxyR，而trxA和trxC受OhrR间接影响。更多的数据表明，谷胱甘肽的缺乏可能是触发trxA和trxC诱导表达的线索。这些发现强调了TRX在细菌OP应激反应中的特殊重要性。重要的是，TRX和GRX系统深度参与细菌对过氧化氢诱导的氧化应激的反应。然而，对它们在其他ROS反应中的作用知之甚少，例如有机过氧化物(OPs)。在本研究中，我们以圆顶单胞菌为研究模型，研究了TrX/GRX和OxyR/OhrR之间的相互作用。我们发现Trxs介导了转录OP反应调节子OhrR的氧化还原状态。虽然trx和grx基因都不受OxyR或OhrR的直接调控，但trxA和trxC的表达是由叔丁基氢过氧化氢(t-BHP)诱导的。我们进一步证明trxA和trxC基因对谷胱甘肽(GSH)耗竭的影响而不是对氧化的反应。这些发现强调了Trx在细菌OP应激反应中的特殊重要性。
The thioredoxin (Trx) and glutaredoxin (Grx) antioxidant systems are deeply involved in bacterial response to oxidative stress, but to date, we know surprisingly little about the roles of these systems in response to reactive oxygen species (ROS) other than hydrogen peroxide (H2O2). In this study, we used Shewanella oneidensis, an environmental bacterium, as a research model to investigate the roles of Trx and Grx in oxidative stress response because it has functionally intertwined ROS responsive regulators OxyR and OhrR. We found that Trx1 is the major thiol/disulfide redox system and that in its absence a Grx system becomes essential under normal conditions. Although overshadowed by Trx1 in the wild type, Trx2 can fully replace Trx1 in physiology when overproduced. Trx1 is required for OxyR to function as a repressor but, more importantly, plays a critical role in the cellular response to organic peroxide (OP) by mediating the redox status of OhrR but not OP scavenger OhrA. While none of the trx and grx genes are OxyR dependent, trxA and trxC are affected by OhrR indirectly. Additional data suggest that depletion of glutathione is likely the cue to trigger induced expression of trxA and trxC. These findings underscore the particular importance of Trx in the bacterial OP stress response.IMPORTANCE The Trx and Grx systems are deeply involved in bacterial responses to H2O2-induced oxidative stress. However, little is known about their roles in response to other ROS, such as organic peroxides (OPs). In this study, we used S. oneidensis as a research model to investigate the interplay between Trx/Grx and OxyR/OhrR. We show that Trxs mediate the redox status of transcriptional OP-responding regulator OhrR. Although none of the trx or grx genes are directly controlled by OxyR or OhrR, expression of trxA and trxC is induced by tert-butyl hydroperoxide (t-BHP). We further show that the trxA and trxC genes respond to effects of glutathione (GSH) depletion rather than oxidation. These findings underscore the particular importance of Trx in the bacterial OP stress response.