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De nombreuses équipes de recherche dans le monde étudient des micro-organismes qualifiés d’extrêmophiles qui, pour certains, vivent en présence de sel à forte concentration (halophiles), pour d’autres à des températures froides ou chaudes (psychrophiles et thermophiles), dans des milieux très acides ou basiques (acidophiles et alcaliphiles) ou sous pression (piézophiles). Ces conditions de vie non conventionnelles nous laissent penser que ces microbes de l’extrême ont mis en place des stratégies originales (enzymes spécifiques) pour s’adapter aux stress physico-chimiques auxquels ils sont confrontés. Plusieurs de ces activités enzymatiques peuvent aujourd’hui trouver des applications en biotechnologie. La plupart des écosystèmes dans lesquels ces organismes se retrouvent sont les marais salants, les sources ou lacs acides ou basiques et les sources géothermales marines terrestres ou sub-terrestres comme les aquifères dits “thermaux” du Bassin Aquitain., Numerous research teams in the world are studying extremophilic micro-organisms, some of them, living at high salt concentrations (halophiles), at cold or hot temperatures (psychrophiles or thermophiles), at low or high pH (acidophiles or alcaliphiles) or under pressure (piezophiles). These unconventional conditions for life suggest that such microbes use original strategies (specific enzymes) to adapt to physico-chemical constraints that they have to face. Several of these enzymatical activities are nowadays good candidates to be used in biotechnological processes. Most of the ecosystems where these organisms are found are marine salterns, acidic and alkaline springs, together with marine, terrestrial or subterrestrial geothermal springs like the deep hot aquifers in the Aquitaine Basin.

Although uranium is a well-characterized nephrotoxic agent, very little is known at the cellular and molecular level about the mechanisms underlying the uptake and toxicity of this element in proximal tubule cells. The aim of this study was thus to characterize the species of uranium that are responsible for its cytotoxicity and define the mechanism which is involved in the uptake of the cytotoxic fraction of uranium using two cell lines derived from kidney proximal (LLC-PK1) and distal (MDCK) tubule as in vitro models. Treatment of LLC-PK1 cells with colchicine, cytochalasin D, concanavalin A and PMA increased the sodium-dependent phosphate co-transport and the cytotoxicity of uranium. On the contrary, replacement of the extra-cellular sodium with N-methyl-d-glucamine highly reduced the transport of phosphate and the cytotoxic effect of uranium. Uranium cytotoxicity was also dependent upon the extra-cellular concentration of phosphate and decreased in a concentration-dependent manner by 0.1-10 mM phosphonoformic acid, a competitive inhibitor of phosphate uptake. Consistent with these observations, over-expression of the rat proximal tubule sodium-dependent phosphate co-transporter NaPi-IIa in stably transfected MDCK cells significantly increased the cytotoxicity of uranium, and computer modeling of uranium speciation showed that uranium cytotoxicity was directly dependent on the presence of the phosphate complexes of uranyl UO2(PO4)- and UO2(HPO4)aq. Taken together, these data suggest that the cytotoxic fraction of uranium is a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate co-transporter system. © 2006 Elsevier Inc. All rights reserved.