Distinct Roles of Shewanella oneidensis Thioredoxin in Regulation of Cellular Responses to Hydrogen and Organic Peroxides.

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 (HO). In this study, we used , 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 and genes are OxyR dependent, and are affected by OhrR indirectly. Additional data suggest that depletion of glutathione is likely the cue to trigger induced expression of and These findings underscore the particular importance of Trx in the bacterial OP stress response. The Trx and Grx systems are deeply involved in bacterial responses to HO-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 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 or genes are directly controlled by OxyR or OhrR, expression of and is induced by -butyl hydroperoxide (-BHP). We further show that the and 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.