PrsQ₂, a small periplasmic protein involved in increased uranium resistance in the bacterium Cupriavidus...

Uranium contamination is a widespread problem caused by natural and anthropogenic activities. Although microorganisms thrive in uranium-contaminated environments, little is known about the actual molecular mechanisms mediating uranium resistance. Here, we investigated the resistance mechanisms driving the adaptation of Cupriavidus metallidurans NA4 to toxic uranium concentrations. We selected a spontaneous mutant able to grow in the presence of 1 mM uranyl nitrate compared to 250 µM for the parental strain. The increased uranium resistance was acquired via the formation of periplasmic uranium-phosphate precipitates facilitated by the increased expression of a genus-specific small periplasmic protein, PrsQ₂, regulated as non-cognate target of the CzcS₂-CzcR₂ two-component system. This study shows that bacteria can adapt to toxic uranium concentrations and explicates the complete genetic circuit behind the adaptation.