The Metabolomic Responses of Caenorhabditis elegans to Cadmium Are Largely Independent of Metallothionein Status, but Dominated by Changes in Cystathionine and Phytochelatins

Cadmium is a widely distributed toxic environmental pollutant. Using proton NMR spectroscopy and UPLC-MS, we obtained metabolic profiles from the model organism Caenorhabditis elegans exposed to sublethal concentrations of cadmium. Neither in the presence nor absence of cadmium did the metallothionein status (single or double mtl knockouts) markedly modulate the metabolic profile. However, independent of strain, cadmium exposure resulted in a decrease in cystathionine concentrations and an increase in the nonribosomally synthesized peptides phytochelatin-2 and phytochelatin-3. This suggests that a primary response to low levels of cadmium is the differential regulation of the C. elegans trans-sulfuration pathway, which channels the flux from methionine through cysteine into phytochelatin synthesis. These results were backed up by the finding that phytochelatin synthase mutants (pcs-1) were at least an order of magnitude more sensitive to cadmium than single or double metallothionein mutants. However, an additive sensitivity toward cadmium was observed in the mtl-1; mtl-2; pcs-1 triple mutant.