Host resistance factor SLC11A1 restricts <i>Salmonella</i> growth through magnesium deprivation.

Abstract

The pleiotropic host resistance factor SLC11A1 (NRAMP1) defends against diverse intracellular pathogens in mammals by yet-unknown mechanisms. We compared <i>Salmonella</i> infection of coisogenic mice with different <i>SLC11A1</i> alleles. SLC11A1 reduced <i>Salmonella</i> replication and triggered up-regulation of uptake systems for divalent metal cations but no other stress responses. SLC11A1 modestly diminished iron availability and acutely restricted <i>Salmonella</i> access to magnesium. Growth of <i>Salmonella</i> cells in the presence of SLC11A1 was highly heterogeneous and inversely correlated with expression of the crucial magnesium transporter gene <i>mgtB</i> We observed superimposable single-cell patterns in mice lacking SLC11A1 when we restricted <i>Salmonella</i> access to magnesium by impairing its uptake. Together, these findings identify deprivation of the main group metal magnesium as the main resistance mechanism of SLC11A1 against <i>Salmonella</i>.