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Host resistance factor SLC11A1 restricts Salmonella growth through magnesium deprivation

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Science  22 Nov 2019:
Vol. 366, Issue 6468, pp. 995-999
DOI: 10.1126/science.aax7898

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Magnesium for Salmonella growth

In mammals, macrophages are a first line of defense against pathogenic bacteria like Salmonella. These immune cells possess a metal-ion transporter called SLC11A1 or NRAMP1, which is known to be involved in infection resistance. Cunrath and Bumann studied mice that only differ in one allele of the SLC11A1 gene, which leaves mice either susceptible or resistant to infection. Proteomic analyses showed that bacteria isolated from mice with functional SLC11A1 alleles experienced metal starvation, particularly of magnesium. The resulting impairment of bacterial growth seems to be the primary mode of action of SLC11A1 against invading pathogens.

Science, this issue p. 995

Abstract

The pleiotropic host resistance factor SLC11A1 (NRAMP1) defends against diverse intracellular pathogens in mammals by yet-unknown mechanisms. We compared Salmonella infection of coisogenic mice with different SLC11A1 alleles. SLC11A1 reduced Salmonella 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 Salmonella access to magnesium. Growth of Salmonella cells in the 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. Together, these findings identify deprivation of the main group metal magnesium as the main resistance mechanism of SLC11A1 against Salmonella.

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