Genome-Wide Transcriptional Response of the Archaeon Thermococcus gammatolerans to Cadmium

Abstract

Thermococcus gammatolerans, the most radioresistant archaeon known to date, is an anaerobic and hyperthermophilic sulfur-reducing organism living in deep-sea hydrothermal vents. Knowledge of mechanisms underlying archaeal metal tolerance in such metal-rich ecosystem is still poorly documented. We showed that T. gammatolerans exhibits high resistance to cadmium (Cd), cobalt (Co) and zinc (Zn), a weaker tolerance to nickel (Ni), copper (Cu) and arsenate (AsO4) and that cells exposed to 1 mM Cd exhibit a cellular Cd concentration of 67 µM. A time-dependent transcriptomic analysis using microarrays was performed at a non-toxic (100 µM) and a toxic (1 mM) Cd dose. The reliability of microarray data was strengthened by real time RT-PCR validations. Altogether, 114 Cd responsive genes were revealed and a substantial subset of genes is related to metal homeostasis, drug detoxification, re-oxidization of cofactors and ATP production. This first genome-wide expression profiling study of archaeal cells challenged with Cd showed that T. gammatolerans withstands induced stress through pathways observed in both prokaryotes and eukaryotes but also through new and original strategies. T. gammatolerans cells challenged with 1 mM Cd basically promote: 1) the induction of several transporter/permease encoding genes, probably to detoxify the cell; 2) the upregulation of Fe transporters encoding genes to likely compensate Cd damages in iron-containing proteins; 3) the induction of membrane-bound hydrogenase (Mbh) and membrane-bound hydrogenlyase (Mhy2) subunits encoding genes involved in recycling reduced cofactors and/or in proton translocation for energy production. By contrast to other organisms, redox homeostasis genes appear constitutively expressed and only a few genes encoding DNA repair proteins are regulated. We compared the expression of 27 Cd responsive genes in other stress conditions (Zn, Ni, heat shock, γ-rays), and showed that the Cd transcriptional pattern is comparable to other metal stress transcriptional responses (Cd, Zn, Ni) but not to a general stress response.

The Confluence of Heavy Metal Biooxidation and Heavy Metal Resistance: Implications for Bioleaching by Extreme Thermoacidophiles

“…Additionally, the cadmium response, along with copper, elicited a defensive stress response including proteins related production and conversion of energy, amino acids biosynthesis, stress responses, and transcription regulation. The results of a general defensive response are consistent with previous characterization and appear to represent a general cellular response to metal challenge [203,242,260,261].…”

Deregulation of transition metals homeostasis is a key feature of cadmium toxicity in Salmonella

“…Since cadmium can interfere also with the homeostasis of other divalent metals (Lagorce et al 2012; Moulis 2010), we have investigated if an impairment in the ability to import iron or manganese could alter Salmonella sensitivity towards cadmium. To this aim we have analyzed the growth curve profiles of mutant strains with significantly altered capability to import iron or manganese (fepA/entF feoB or sitABCD mntH) in presence or absence of cadmium.…”

“…Besides inducing the upregulation of the ZntA detoxification system, several observations indicate that cadmium enhances transcription of genes involved in the response to zinc deficiency (Wang and Crowley 2005;Joe et al 2011;Lagorce et al 2012;Maynaud et al 2013). This response is controlled by Zur, a zinc-binding protein which regulates the transcription of a small number of genes encoding for proteins enabling bacteria to respond to zinc starvation, including the high affinity zinc importer ZnuABC (Patzer and Hantke 1998).…”

Molecular Characterization of Copper and Cadmium Resistance Determinants in the Biomining Thermoacidophilic ArchaeonSulfolobus metallicus

“…These high similarities suggest that Cd export may be a common resistance mechanism among acidophiles [11]. Recently, a time-dependent transcriptomic analysis using microarrays in the radioresistant archaeon Thermococcus gammatolerans cells exposed to Cd showed the induction of genes related to metal homeostasis, drug detoxification, reoxidation of cofactors, ATP production, and DNA repair [27]. …”