FIGURE 1.

Metal transporters combat infection. Panel A highlights metals within the periodic table of elements that have been studied as potential substrates for Nramp1 and/or DMT1. Panel B shows a structural homology model with 12 transmembrane-spanning domains representing two pseudo-symmetric halves. The loop between membrane domains 7–8 has been topologically determined to face the extracellular milieu. Also indicated is the proximity of Gly-169 and Gly-185 residues in the fourth transmembrane domain (cross-mark). Amino acid substitutions at this site in mice and rats disable transport function and stability of the membrane transporters Nramp1 and DMT1, respectively. Panel C depicts the cellular localizations of iron and manganese transporters that may provide host resistance as discussed in the text. Panel D outlines the double-edged sword of iron transport. As iron levels increase, the susceptibility to pathogen growth and virulence is known to increase with decreasing survival of host. Conversely, iron depletion disables the appropriate inflammatory response necessary for NO production and cytokine expression.