The Fur iron regulator-like protein is cryptic in the hyperthermophilic archaeonThermococcus kodakaraensis

Abstract

Archaea, which regroup organisms with extreme living conditions, possess many predicted iron-containing proteins that may be metabolically critical; however, their need for iron remains poorly documented. In this report, iron acquisition mechanisms were investigated in the hyperthermophilic archaeon Thermococcus kodakaraensis. Thermococcus kodakaraensis requires iron for its growth and possesses many putative iron uptake systems, including several ATP-binding cassette-like transporters and two FeoAB-like receptors, showing that this organism shares similar features with bacteria. One homolog of the major bacterial iron regulator, ferric uptake regulator (Fur), with about 50% similarity to Escherichia coli Fur was also identified. Thermococcus kodakaraensis Fur was found to be able to specifically bind to a Fur-binding site consensus-like sequence of its own gene promoter. However, its expression has been hindered by a -1 frameshift mutation and the chromosomal repair of this mutation did not affect T. kodakaraensis in vivo phenotypes. Microarrays analyses helped to further characterize T. kodakaraensis iron-dependent growth and revealed no role for the Fur homolog in the global regulatory response of the cells to iron. In contrast, additional evidences indicated that the T. kodakaraensis diphtheria toxin regulator (DtxR) homolog may control the expression of the major iron acquisition effectors, while its inactivation enabled higher resistance to iron deficiency.

Regulation of Iron Metabolism by Pyrococcus furiosus

“…However, in an anaerobic environment, iron is expected to remain mostly in the ferrous form, which is readily soluble and accessible, and the likelihood of oxidative damage is minimized. It has been reported that the global transcription profiles of the hyperthermophilic archaeon Thermococcus kodakarensis, a close relative of P. furiosus, were similar under iron-sufficient and iron-limited conditions, suggesting a lessthan-stringent response to iron availability (14). Similar nonresponsive transcriptional effects of iron were also observed with the obligately anaerobic and mesophilic bacteria Coxiella burnetii and Dichelobacter nodosus (15,16).…”

“…The DtxR in T. kodakarensis is a potential regulator of the production of FeoAB and ferritin according to transcriptional analysis of a deletion mutant. However, the DtxR protein does not bind to the promoters of feoAB or ferritin genes based on electrophoretic mobility shift assays (14). In contrast, and for unknown reasons, Fur is poorly conserved in the Thermococcaceae, as it is found only in P. furiosus, Thermococcus barophilus (82% similarity to P. furiosus Fur), and T. kodakarensis (86% similarity to P. furiosus Fur).…”

Transcriptional factor Fur from Thermoplasma volcanium binds its own promoter DNA in a divalent cation-dependent manner

“…However, T. kodakaraensis Fur is not able to bind to the TATA-box but rather to a palindromic sequence, 5 -CTATTTAGAAAT-A-ATTTCTAATTAG-3 , located upstream of the TATAbox. Furthermore, the binding of T. kodakaraensis Fur is not iron-dependent and it is probably inactivated by a 1 frameshift (Louvel et al, 2009) in vivo. In E. coli, Fur controls the iron-dependent expression not only of genes involved in iron acquisition but also genes for iron-independent function such as respiration, motility, metabolism, tricarboxylic acid cycle (Stojiljkovic et al, 1994;Vassinova and Kozyruv, 2000), resistance to redox stress (Niederhoffer et al, 1990;Touati, 1988), and a small noncoding RNA, RyhB (Wassarman et al, 2001).…”

“…In E. coli, Fur controls the iron-dependent expression not only of genes involved in iron acquisition but also genes for iron-independent function such as respiration, motility, metabolism, tricarboxylic acid cycle (Stojiljkovic et al, 1994;Vassinova and Kozyruv, 2000), resistance to redox stress (Niederhoffer et al, 1990;Touati, 1988), and a small noncoding RNA, RyhB (Wassarman et al, 2001). Although the DtxR family transcriptional repressor represents an adaptation to iron defi ciency in T. kodakaraensis (Louvel et al, 2009), Fur is an important factor for iron homeostasis in archaea as well as bacteria.…”

“…Genes under Fur control have been identifi ed in those bacteria and in several other organisms (Escolar et al, 1999). In archaea, a Fur homologue of hyperthermophilic archaeon Thermococcus kodakaraensis was investigated (Louvel et al, 2009); however, the relationship between transcriptional regulation by Fur and the availability of iron or divalent cations in their environment remains unclear.…”