Cadmium and Copper Cross-Tolerance. Cu Alleviates Cd Toxicity, and Both Cations Target Heme and Chlorophyll Biosynthesis Pathway in .

Cadmium, although not redox active is highly toxic. Yet, the underlying mechanisms driving toxicity are still to be characterized. In this study, we took advantage of the purple bacterium strain with defective Cd-efflux system to identify targets of this metal. Exposure of the Δ strain to Cd causes a decrease in the photosystem amount and in the activity of respiratory complexes. As in case of Cu toxicity, the data indicated that Cd targets the porphyrin biosynthesis pathway at the level of HemN, a -adenosylmethionine and CxxxCxxC coordinated [4Fe-4S] containing enzyme. Cd exposure therefore results in a deficiency in heme and chlorophyll dependent proteins and metabolic pathways. Given the importance of porphyrin biosynthesis, HemN represents a key metal target to account for toxicity. In the environment, microorganisms are exposed to mixture of metals. Nevertheless, the biological effects of such mixtures, and the toxicity mechanisms remain poorly addressed. To highlight a potential cross-talk between Cd and Cu -efflux systems, we show (i) that Cd induces the expression of the Cd-efflux pump and the Cu detoxification system CopA and CopI; and (ii) that Cu ions improve tolerance towards Cd, demonstrating thus that metal mixtures could also represent a selective advantage in the environment.