Genomic and transcriptomic analyses reveal insights into cadmium resistance mechanisms of Cupriavidus nantongensis E324
The cadmium-resistant Cupriavidus  sp. E324 strain has been previously shown to have a high potential  for use in cadmium (Cd) remediation,  due to its high capacity for  cadmium bioaccumulation. According to the comparative genomic analysis, the E324 strain was  most closely related to C.  nantongensis X1 T , indicating that the E324 strain should be re-identified as C. nantongensis. To unravel the Cd tolerance mechanisms of  C. nantongensis E324,  the transcriptional response of this strain to Cd stress was assessed using RNA-seq-based transcriptome analysis,  followed by validation through qRT- PCR. The results showed that the upregulated Differentially Expressed Genes (DEGs) were significantly enriched in categories related to  metal binding and transport, phosphate transport, and oxidative stress response. Consistently, we observed significant increases in both the cell wall and intracellular contents of certain essential metals (Cu, Fe, Mn, and Zn) upon Cd exposure). Among these, only the Zn pretreatment resulting in  high Zn accumulation in the cell walls could enhance bacterial growth under Cd stress conditions through its role in inhibiting Cd accumulation. Additionally, the promotion of catalase activity and glutathione metabolism upon Cd exposure to cope with Cd-induced oxidative stress was demonstrated. Meanwhile, the  upregulation of phosphate transport-related genes upon Cd treatment seems to be the bacterial response to Cd-induced phosphate depletion. Altogether, our findings suggest that these adaptive responses are critical mechanisms contributing to increased Cd tolerance in C. nantongensis E324 strain via the enhancement of metal-chelating and antioxidant capacities of the cells. Overall design: To investigate the Cd tolerance mechanism in C. nantongensis E324, we examined the transcriptome profile of this strain in response to Cd exposure. We analyzed the sequencing data for six samples: three treated with 4 mM CdCl2 and three control samples without CdCl2 treatment