Heterogeneous dual-metal control ofSalmonellainfection

Abstract

AbstractIron controls bacterial infections through diverse pathogen and host mechanisms that remain challenging to disentangle. Here, we determined how individualSalmonellacells access iron in infected mice. Our results showed that the iron transporter SLC11A1 restricted iron availability. However, manySalmonellabypassed this restriction by targeting macrophage endosomes that contained remnants of iron-rich red blood cells. These iron-replete bacteria dominated overallSalmonellagrowth 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 controllingSalmonella, 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 summaryIron and magnesium limitations control distinctSalmonellasubsets during infection.