Heterogeneous dual-metal control of Salmonella infection

Iron controls bacterial infections through diverse pathogen and host mechanisms that remain challenging to disentangle. Here, we determined how individual Salmonella cells access iron in infected mice. Our results showed that the iron transporter SLC11A1 restricted iron availability. However, many Salmonella bypassed this restriction by targeting macrophage endosomes that contained remnants of iron-rich red blood cells. These iron-replete bacteria dominated overall Salmonella growth and masked the relieve of iron-starved bacteria under iron overload. These data, combined with our previous discovery of magnesium deprivation as a primary mechanism for controlling Salmonella , reveal a heterogeneous dual-metal mechanism of nutritional immunity, and highlight the power of single-cell analyses under physiological in-vivo conditions to unravel complex anti-bacterial host mechanisms. One sentence summary Iron and magnesium limitations control distinct Salmonella subsets during infection. ### Competing Interest Statement The authors have declared no competing interest.