Divalent-metal transport by NRAMP proteins at the interface of host-pathogen interactions

The NRAMP family of divalent-metal transporters plays a key role in the homeostasis of iron and other metals. NRAMP2 (DMT1) acts as an iron-uptake protein in both the duodenum and in peripheral tissues. NRAMP1 functions as a divalent-metal eff lux pump at the phagosomal membrane of macrophages and neutrophils, and mutations in NRAMP1 cause susceptibility to several intracellular pathogens. NRAMP homologues have been identified in bacteria and are involved in acquiring divalent metals from the extracellular environment. Interestingly, bacterial and mammalian NRAMP proteins would compete for the same essential substrates within the microenvironment of the phagosome, at the interface of host-pathogen interactions.