Updated project metadata. Cadmium is one of several heavy metals present in contaminated soils. Apparently, it has no biological role but can produce DNA damage, overexpression of stress response proteins and misfolded proteins, amongst other deleterial effects. Acidithiobacillus ferrooxidans is an acidophilic bacterium capable of resisting very high concentrations of heavy metals such as cadmium. This is important for industrial bioleaching processes where Cd+2 concentrations can be in the range of 5-100 mM. Cadmium resistance mechanisms in these microorganisms have not been fully characterized. A. ferrooxidans ATCC 53993 contains genes coding for possible metal resistance determinants such as efflux systems belonging to three families: P-type ATPases, RND transporters and cation diffusion facilitators (CDF). In addition, it has some extra copies of these genes in its exclusive genomic island (GI). Several of these putative genes were characterized in the present report by determining their transcriptional expression profiles and functionality. Moreover, a global quantitative proteomic analysis was carried out to further explore new cadmium resistance determinants in this biomining acidophile. Changes in iron oxidation pathways, upregulation of transport proteins (P-type ATPases and CDFs) and changes in ribosomal protein levels were seen. Finally, increased concentrations of exclusive putative cadmium ATPases present in strain ATCC 53993 GI and other non-identified proteins such as Lferr_0210, which forms part of a possible operon, could explain its greater resistance to cadmium compared to other acidophiles such as A. ferrooxidans ATCC 23270.