Increasing the copper sensitivity of microorganisms by restricting iron supply, a strategy for bio-management practices.

Pollution by copper (Cu2+ ) extensively used as antimicrobial in agriculture and farming represents a threat to the environment and human health. Finding ways to make microorganisms sensitive to lower metal concentrations could help decreasing the use of Cu2 + in agriculture. In this respect, we showed that limiting iron (Fe) uptake makes bacteria much more susceptible to Cu2 + or Cd2+ poisoning. Using efflux mutants of the purple bacterium Rubrivivax gelatinosus, we showed that Cu+ and Cd2+ resistance relies on the expression of the Fur-regulated FbpABC and Ftr iron transporters. To support this conclusion, inactivation of these Fe-importers in the Cu+ or Cd2+ -ATPase efflux mutants gave rise to hypersensitivity towards these ions. Moreover, in metal overloaded cells the expression of FbpA, the periplasmic iron-binding component of the ferric ion transport FbpABC system was induced, suggesting that cells perceived an 'iron-starvation' situation and responded to it by inducing Fe-importers. In this context, the Fe-Sod activity increased in response to Fe homoeostasis dysregulation. Similar results were obtained for Vibrio cholerae and Escherichia coli, suggesting that perturbation of Fe-homoeostasis by metal excess appeared as an adaptive response commonly used by a variety of bacteria. The presented data support a model in which metal excess induces Fe-uptake to support [4Fe-4S] synthesis and thereby induce ROS detoxification system.