BacteROS

Hydrogen peroxide, H2O2 is a key component of host-microbe interaction. However H2O2 concentrations generated by immune cells or epithelia are usually insufficient for bacterial killing, and rather modulate bacterial responses. Here we investigated the impact of sublethal H2O2 concentration on gene expression of E.coli BW25113 after an exposure of 10 and 60 minutes. RNA-seq analysis revealed that approximately 12% of E. coli genes were strongly dysregulated 10 minutes following exposure to 2.5 mM H2O2. H2O2 exposure led to the activation of specific antioxidant responses but also general stress responses characterized by a transient downregulation of genes involved in growth-related functions such as nucleic acid biosynthesis and translation with a striking and coordinated downregulation of genes involved in ribosome formation, and a sustained upregulation of the SOS response. We confirmed the rapid, transient and specific response mediated by the transcription factor OxyR leading to upregulation of antioxidant systems, including the catalase (katG), which rapidly degraded extracellular H2O2 and promoted bacterial survival. We documented a strong and transient upregulation of genes involved in sulfur metabolism and cysteine biosynthesis, which are under the control of the transcription factor CysB. However, this strong specific transcriptional response to H2O2 has no apparent direct impact on bacterial survival, but possibly aims at replenishing the stores of oxidized cysteines and glutathione. In summary, our results demonstrate that different stress responses mechanisms are activated by H2O2 exposure and highlight the cysteine synthesis as a new antioxidant response in E.coli.