title: Snapshot of iron response in Shewanella oneidensis by gene network reconstruction.
abstract: BACKGROUND
  Iron homeostasis of Shewanella oneidensis, a gamma-proteobacterium possessing high iron content, is regulated by a global transcription factor Fur. However, knowledge is incomplete about other biological pathways that respond to changes in iron concentration, as well as details of the responses. In this work, we integrate physiological, transcriptomics and genetic approaches to delineate the iron response of S. oneidensis.
  
  
  RESULTS
  We show that the iron response in S. oneidensis is a rapid process. Temporal gene expression profiles were examined for iron depletion and repletion, and a gene co-expression network was reconstructed. Modules of iron acquisition systems, anaerobic energy metabolism and protein degradation were the most noteworthy in the gene network. Bioinformatics analyses suggested that genes in each of the modules might be regulated by DNA-binding proteins Fur, CRP and RpoH, respectively. Closer inspection of these modules revealed a transcriptional regulator (SO2426) involved in iron acquisition and ten transcriptional factors involved in anaerobic energy metabolism. Selected genes in the network were analyzed by genetic studies. Disruption of genes encoding a putative alcaligin biosynthesis protein (SO3032) and a gene previously implicated in protein degradation (SO2017) led to severe growth deficiency under iron depletion conditions. Disruption of a novel transcriptional factor (SO1415) caused deficiency in both anaerobic iron reduction and growth with thiosulfate or TMAO as an electronic acceptor, suggesting that SO1415 is required for specific branches of anaerobic energy metabolism pathways.
  
  
  CONCLUSIONS
  Using a reconstructed gene network, we identified major biological pathways that were differentially expressed during iron depletion and repletion. Genetic studies not only demonstrated the importance of iron acquisition and protein degradation for iron depletion, but also characterized a novel transcriptional factor (SO1415) with a role in anaerobic energy metabolism.
authors.affiliation: Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. yangy@ornl.gov
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Yang
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Harris
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.forename: Wenlu
authors.initials: W
authors.lastname: Xiong
authors.forename: Marcin
authors.initials: M
authors.lastname: Joachimiak
authors.forename: Liyou
authors.initials: L
authors.lastname: Wu
authors.forename: Paramvir
authors.initials: P
authors.lastname: Dehal
authors.forename: Janet
authors.initials: J
authors.lastname: Jacobsen
authors.forename: Zamin
authors.initials: Z
authors.lastname: Yang
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Palumbo
authors.forename: Adam P
authors.initials: AP
authors.lastname: Arkin
authors.forename: Jizhong
authors.initials: J
authors.lastname: Zhou