Beyond the Fur paradigm: iron-controlled gene expression in rhizobia.
ABSTRACT Iron is critical for bacterial growth, but problems arise from the toxicity of excess iron; thus, iron uptake is subject to tight control. The most widely found and best-studied iron-responsive regulator in Gram-negative bacteria is the ferric uptake regulator Fur. In recent years, however, it has become apparent that iron regulation in rhizobia differs from that in many other bacteria. New regulators (RirA, Irr, Mur) were identified which appear to mediate functions that in other bacteria are accomplished by Fur. Even though some of them belong to the Fur family, they exhibit properties that clearly separate them from genuine Fur proteins. This article surveys the principal mechanisms of iron acquisition and uptake in rhizobia, and puts particular emphasis on recent findings on transcriptional regulators and their means to sense the cellular iron status and to regulate gene expression. In this context, we point out differences and similarities with regard to the operators, regulons and structure of the discussed iron regulatory proteins.
Article: Fur controls iron homeostasis and oxidative stress defense in the oligotrophic alpha-proteobacterium Caulobacter crescentus.[show abstract] [hide abstract]
ABSTRACT: In most bacteria, the ferric uptake regulator (Fur) is a global regulator that controls iron homeostasis and other cellular processes, such as oxidative stress defense. In this work, we apply a combination of bioinformatics, in vitro and in vivo assays to identify the Caulobacter crescentus Fur regulon. A C. crescentus fur deletion mutant showed a slow growth phenotype, and was hypersensitive to H(2)O(2) and organic peroxide. Using a position weight matrix approach, several predicted Fur-binding sites were detected in the genome of C. crescentus, located in regulatory regions of genes not only involved in iron uptake and usage but also in other functions. Selected Fur-binding sites were validated using electrophoretic mobility shift assay and DNAse I footprinting analysis. Gene expression assays revealed that genes involved in iron uptake were repressed by iron-Fur and induced under conditions of iron limitation, whereas genes encoding iron-using proteins were activated by Fur under conditions of iron sufficiency. Furthermore, several genes that are regulated via small RNAs in other bacteria were found to be directly regulated by Fur in C. crescentus. In conclusion, Fur functions as an activator and as a repressor, integrating iron metabolism and oxidative stress response in C. crescentus.Nucleic Acids Research 07/2009; 37(14):4812-25. · 8.03 Impact Factor
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ABSTRACT: Because iron toxicity and deficiency are equally life threatening, maintaining intracellular iron levels within a narrow optimal range is critical for nearly all known organisms. However, regulatory mechanisms that establish homeostasis are not well understood in organisms that dwell in environments at the extremes of pH, temperature, and salinity. Under conditions of limited iron, the extremophile Halobacterium salinarum, a salt-loving archaeon, mounts a specific response to scavenge iron for growth. We have identified and characterized the role of two transcription factors (TFs), Idr1 and Idr2, in regulating this important response. An integrated systems analysis of TF knockout gene expression profiles and genome-wide binding locations in the presence and absence of iron has revealed that these TFs operate collaboratively to maintain iron homeostasis. In the presence of iron, Idr1 and Idr2 bind near each other at 24 loci in the genome, where they are both required to repress some genes. By contrast, Idr1 and Idr2 are both necessary to activate other genes in a putative a feed forward loop. Even at loci bound independently, the two TFs target different genes with similar functions in iron homeostasis. We discuss conserved and unique features of the Idr1-Idr2 system in the context of similar systems in organisms from other domains of life.Nucleic Acids Research 11/2010; 39(7):2519-33. · 8.03 Impact Factor
Article: ROS-Mediated Signalling in Bacteria: Zinc-Containing Cys-X-X-Cys Redox Centres and Iron-Based Oxidative Stress.[show abstract] [hide abstract]
ABSTRACT: Bacteria are permanently in contact with reactive oxygen species (ROS), both over the course of their life cycle as well that present in their environment. These species cause damage to proteins, lipids, and nucleotides, negatively impacting the organism. To detect these ROS molecules and to stimulate the expression of proteins involved in antioxidative stress response, bacteria use a number of different protein-based regulatory and sensory systems. ROS-based stress detection mechanisms induce posttranslational modifications, resulting in overall conformational and structural changes within sensory proteins. The subsequent structural rearrangements result in changes of protein activity, which lead to regulated and appropriate response on the transcriptional level. Many bacterial enzymes and regulatory proteins possess a conserved signature, the zinc-containing redox centre Cys-X-X-Cys in which a disulfide bridge is formed upon oxidative stress. Other metal-dependent oxidative modifications of amino acid side-chains (dityrosines, 2-oxo-histidines, or carbonylation) also modulate the activity of redox-sensitive proteins. Using molecular biology, biochemistry, biophysical, and structure biology tools, molecular mechanisms involved in sensing and response to oxidative stress have been elucidated in detail. In this review, we analyze some examples of bacterial redox-sensing proteins involved in antioxidative stress response and focus further on the currently known molecular mechanism of function.Journal of signal transduction. 01/2012; 2012:605905.