Updated project metadata. The toxicity of the heavy metal cadmium is well established. However, the molecular basis for how this toxicity perturbs cellular viability is still not well understood. This project investigates the cellular and molecular impacts of cadmium stress in the bacterial pathogen, Streptococcus pneumoniae. We find that cadmium depletes cellular manganese and zinc stores, leading to disruption of metalloproteins and the corresponding biochemical pathways. Furthermore, the over-accumulation of cadmium within the cells appears to facilitate mismetallation events, whereby native metal cofactors are displaced by cadmium, leading to reduced or abrogated enzymatic activity. These metalloproteomic analyses have been conducted in conjunction with transcriptomics and metabolomics to elucidate the global impacts of cadmium stress within a prokaryotic organism.