Abstract
BackgroundPrevious work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Dynamic alteration of the gene regulatory network (GRN) has been implicated in such resistance. However, the molecular functions of transcription regulatory proteins involved in this response remain unknown.ResultsHere we have reanalyzed several existing GRN and systems biology datasets for H. salinarum to identify and characterize a novel winged helix-turn-helix transcription factor, VNG0258H, as a regulator required for reactive oxygen species resistance in this organism. This protein appears to be unique to the haloarchaea at the primary sequence level. High throughput quantitative growth assays in a deletion mutant strain implicate VNG0258H in extreme oxidative stress resistance. According to time course gene expression analyses, this transcription factor is required for the appropriate dynamic response of nearly 300 genes to reactive oxygen species damage from paraquat and hydrogen peroxide. These genes are predicted to function in repair of oxidative damage to proteins and DNA. In vivo DNA binding assays demonstrate that VNG0258H binds DNA to mediate gene regulation.ConclusionsTogether these results suggest that VNG0258H is a novel archaeal transcription factor that regulates gene expression to enable adaptation to the extremely oxidative, hypersaline niche of H. salinarum. We have therefore renamed VNG0258H as RosR, for reactive oxygen species regulator.
Highlights
Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation
Using existing systems biology datasets to identify candidate regulators of reactive oxygen species (ROS) stress response To identify transcription regulatory proteins involved in the response to ROS and/or oxygen-related physiology in H. salinarum, we mined the existing systems biology datasets for this organism to identify candidate transcription factors
We reasoned that slight differences in the expression profiles of transcription factors (TFs) within the same node may not have been detected by the inference procedure, but may become evident upon closer inspection
Summary
Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Halobacterium salinarum, an extremely halophilic euryarchaeon that resides in salt lakes and marine salterns, requires nearly saturated salt for growth and survival (100–150 g/L) [1] In these environments, UV damage from intense sunlight and desiccation-rehydration cycles generate high levels of reactive oxygen species (ROS) and damage DNA and proteins [2]. Like other ROS-resistant microbes such as Deinococcus radiodurans, H. salinarum uses a battery of enzymatic and non-enzymatic strategies to withstand macromolecular damage These include functional redundancy of DNA repair and antioxidant enzyme-coding genes [4,5,6]; a high cytosolic Mn(II) to Fe (III) ratio [7,8,9]; genomic polyploidy to provide templates for DNA double strand break repair [10]; and differential regulation of genes encoding macromolecular repair functions in response to oxidative stress [11]. The molecular functions of these putative ROS-responsive regulators remain unclear in this organism and other archaeal species
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