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

Pollution by copper (Cu(2+)) 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 Cu(2) (+) in agriculture. In this respect, we showed that limiting iron (Fe) uptake makes bacteria much more susceptible to Cu(2) (+) or Cd(2+) poisoning. Using efflux mutants of the purple bacterium Rubrivivax gelatinosus, we showed that Cu(+) and Cd(2+) 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 Cd(2+)‐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.