Bacteria respond to metal pollution through sensors that control the uptake and the detoxification machineries. Specificity in metal recognition is therefore a prerequisite for triggering the appropriate response, particularly when facing a mixture of metals. In response to Cu+, the purple bacterium Rubrivivax gelatinosus induces the efflux Cu+-ATPase CopA by the Cu+ regulator CopR. However, genetic analyses have suggested the presence of additional regulators. Here, we show that CadR, the Cd2+ sensor, is involved in Cd2+ and Cu+ tolerance and demonstrate that CopR and CadR share common target genes. Interestingly, expression of the Cu+ detoxification and efflux (CopI/CopA) system was induced by Cd2+ and downregulated in the double mutant copRcadR-. This double mutant was more sensitive to low Cu+ concentration than the single copR- mutant, and accumulation of coproporphyrin III pointed to a significantly decreased expression of CopA. Furthermore, analyses of Cd2+ toxicity in the cadR- mutant suggested that although CopR is Cu+ selective, CopR is involved in Cd2+ response since the addition of Cu+ alleviates Cd2+ toxicity. Based on our current knowledge of metal transport across the inner membrane, Cd2+ and Cu+ do not share common efflux routes nor do they share common regulators. Nevertheless, the crosstalk between Cd2+ and Cu+ tolerance systems is demonstrated in the present study. The modulation of Cu+ detoxification by a Cd2+ regulator in vivo places emphasis on the relaxed selectivity, under elevated metal concentration, in MerR regulators.
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