When Two'S Company: New Evidences On Dual Fe/Co Selectivity Of Transport In The Co2+-Exporting Cation Diffusion Facilitators (Cof-Ecdf) Family

Different families of bacterial membrane transporters selectively catalyze the efflux of transition metals (TMs). This is a mechanism to avoid intracellular TM accumulation that would lead to oxidative damage and cell death. In the N2-fixating bacteria Sinorhizobium meliloti, a deletion mutant of the Cation Diffusion Facilitator exporter family member AitP (Smc04167) showed Co2+ sensitivity and Fe2+ and Co2+ accumulation. Both TM levels were restored after reintroducing the mutated gene. Iron sensitivity was detected in a double mutant lacking aitP and the membrane bound ferritin A (mbfA) and this paralleled a higherFe2+ accumulation. Kinetic analysis of Fe2+ transport into everted membranes vesicles of E. coli overexpressing AitP showed a H+-electrochemical gradient dependent and saturable Fe2+ transport, with a low Fe2+ affinity as expected for detoxification exporters. Transcriptions of aitP and Smc04168, the putative FrmR-like transcriptional factor gene upstream, were induced by Co2+ presence in the media. Integrating our new results to the previous characterization of ortholog members of AitP as Co2+ exporters regulated by FrmR-like factors (CoF-eCDF), we propose a double Fe/Co specificity of transport for this sub-family and speculate that this dual function contributes to an early and rapid adaptation in different scenarios where Co2+ acts as a toxic agent. We then propose to reclassify this sub-family of exporters as CoFFe-eCDFs.