Using the bacterium Escherichia coli as a model, researchers at our laboratory are working to identify potential targets of and the molecular mechanisms underpinning cobalt toxicity.

Working alongside a bacterial microbiology team from the CNRS unit in Marseille (UPR-CNRS 9043), the researchers have demonstrated in vivo cobalt deactivation inactivation of a number of essential iron-sulfphur cluster proteins. Cobalt tolerance requires the involvement of proteins belonging to the SUF system, the iron-sulfphur cluster biosynthetic mechanism that is particularly active under conditions of stress (oxidative stress or iron deficiency). In vitro studies have also revealed that cobalt does not react directly with previously assembled iron-sulfphur clusters, but rather with the labile iron-sulfphur clusters found in the scaffold proteins involved in iron-sulfphur cluster biosynthesis.

These findings support the hypothesis that cobalt inhibits the biosynthesis and/or repair of iron-sulfphur clusters by competing directly with iron at the relevant sites.

The results of this research, which was carried out under the ToNuc-E programme, illustrate the key role of iron-sulfphur cluster biogenesis within cells.