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Snapshot of iron response in Shewanella oneidensis by gene network reconstruction.

Yang Y, Harris DP, Luo F, Xiong W, Joachimiak M, Wu L, Dehal P, Jacobsen J, Yang Z, Palumbo AV, Arkin AP, Zhou J - BMC Genomics (2009)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. yangy@ornl.gov

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.

Conclusion: 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.

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(A) Module of iron acquisition systems. Each node represents a gene and the width of the line represents the correlation coefficient of two linked genes. Blue and gray lines indicate positive and negative correlation coefficients, respectively. Colors are assigned to nodes according to their functional categories: red represents known iron acquisition systems, lavender represents transcriptional regulator, white represents unknown genes, and the black node depicts a gene whose association to other genes is not yet understood. The sequence logo of the consensus sequence in the promoter regions of genes in the module of iron acquisition systems was generated by the Gibbs Recursive Sampler program [28] and Weblogo program [50]. (B) Module of genes related to anaerobic energy metabolism. Colors are assigned as described in Fig. 3A except that red nodes represent genes with known roles in anaerobic energy metabolism. (C) Module of genes involved in protein degradation. Colors are assigned to nodes according to their functional categories: red represents genes that function in protein degradation, and white represents genes with unknown function.
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Figure 3: (A) Module of iron acquisition systems. Each node represents a gene and the width of the line represents the correlation coefficient of two linked genes. Blue and gray lines indicate positive and negative correlation coefficients, respectively. Colors are assigned to nodes according to their functional categories: red represents known iron acquisition systems, lavender represents transcriptional regulator, white represents unknown genes, and the black node depicts a gene whose association to other genes is not yet understood. The sequence logo of the consensus sequence in the promoter regions of genes in the module of iron acquisition systems was generated by the Gibbs Recursive Sampler program [28] and Weblogo program [50]. (B) Module of genes related to anaerobic energy metabolism. Colors are assigned as described in Fig. 3A except that red nodes represent genes with known roles in anaerobic energy metabolism. (C) Module of genes involved in protein degradation. Colors are assigned to nodes according to their functional categories: red represents genes that function in protein degradation, and white represents genes with unknown function.

Mentions: The large module shown in Fig. 3A is composed almost exclusively of iron acquisition systems, suggesting that these genes are highly co-regulated under iron depletion and repletion conditions. These genes include the TonB system (TonB1-ExbB1-ExbD1), the hemin ABC transporter (HmuT, HmuU and HmuV), the siderophore synthetic protein (AlcA), and an iron-regulated outer membrane protein (IrgA). A majority of genes were strongly induced by iron depletion and repressed by iron repletion (see Table 3 for details). Notably, two homologous TonB systems located at the inner membrane have been annotated in S. oneidensis. The TonB1-exbB1-exbD1 operon was induced 2.4–64.6 fold during iron depletion and then repressed up to 100 fold by iron repletion, while TonB2-exbB2-exbD2 was not regulated by iron. Consistently, a "Fur box" was identified upstream of the TonB1-exbB1-exbD1 operon, but not upstream of the TonB2-exbB2-exbD2 operon [3]. In contrast, three genes (Bfr2, SO3065 and SuhB) display expression patterns opposite to the iron acquisition systems (Fig. 3A). The presence of Bfr2 can be explained as a bacterioferritin subunit that is regulated in the opposite way to iron acquisition.


Snapshot of iron response in Shewanella oneidensis by gene network reconstruction.

Yang Y, Harris DP, Luo F, Xiong W, Joachimiak M, Wu L, Dehal P, Jacobsen J, Yang Z, Palumbo AV, Arkin AP, Zhou J - BMC Genomics (2009)

(A) Module of iron acquisition systems. Each node represents a gene and the width of the line represents the correlation coefficient of two linked genes. Blue and gray lines indicate positive and negative correlation coefficients, respectively. Colors are assigned to nodes according to their functional categories: red represents known iron acquisition systems, lavender represents transcriptional regulator, white represents unknown genes, and the black node depicts a gene whose association to other genes is not yet understood. The sequence logo of the consensus sequence in the promoter regions of genes in the module of iron acquisition systems was generated by the Gibbs Recursive Sampler program [28] and Weblogo program [50]. (B) Module of genes related to anaerobic energy metabolism. Colors are assigned as described in Fig. 3A except that red nodes represent genes with known roles in anaerobic energy metabolism. (C) Module of genes involved in protein degradation. Colors are assigned to nodes according to their functional categories: red represents genes that function in protein degradation, and white represents genes with unknown function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667191&req=5

Figure 3: (A) Module of iron acquisition systems. Each node represents a gene and the width of the line represents the correlation coefficient of two linked genes. Blue and gray lines indicate positive and negative correlation coefficients, respectively. Colors are assigned to nodes according to their functional categories: red represents known iron acquisition systems, lavender represents transcriptional regulator, white represents unknown genes, and the black node depicts a gene whose association to other genes is not yet understood. The sequence logo of the consensus sequence in the promoter regions of genes in the module of iron acquisition systems was generated by the Gibbs Recursive Sampler program [28] and Weblogo program [50]. (B) Module of genes related to anaerobic energy metabolism. Colors are assigned as described in Fig. 3A except that red nodes represent genes with known roles in anaerobic energy metabolism. (C) Module of genes involved in protein degradation. Colors are assigned to nodes according to their functional categories: red represents genes that function in protein degradation, and white represents genes with unknown function.
Mentions: The large module shown in Fig. 3A is composed almost exclusively of iron acquisition systems, suggesting that these genes are highly co-regulated under iron depletion and repletion conditions. These genes include the TonB system (TonB1-ExbB1-ExbD1), the hemin ABC transporter (HmuT, HmuU and HmuV), the siderophore synthetic protein (AlcA), and an iron-regulated outer membrane protein (IrgA). A majority of genes were strongly induced by iron depletion and repressed by iron repletion (see Table 3 for details). Notably, two homologous TonB systems located at the inner membrane have been annotated in S. oneidensis. The TonB1-exbB1-exbD1 operon was induced 2.4–64.6 fold during iron depletion and then repressed up to 100 fold by iron repletion, while TonB2-exbB2-exbD2 was not regulated by iron. Consistently, a "Fur box" was identified upstream of the TonB1-exbB1-exbD1 operon, but not upstream of the TonB2-exbB2-exbD2 operon [3]. In contrast, three genes (Bfr2, SO3065 and SuhB) display expression patterns opposite to the iron acquisition systems (Fig. 3A). The presence of Bfr2 can be explained as a bacterioferritin subunit that is regulated in the opposite way to iron acquisition.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. yangy@ornl.gov

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.

Conclusion: 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.

Show MeSH