Host resistance factor SLC11A1 restricts Salmonella growth through magnesium deprivation

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