How pathogens feel and overcome magnesium limitation when in host tissues Original paper

What was reviewed?

This review explained how hosts use nutritional immunity to restrict pathogen growth and why magnesium limitation is a special case, because Mg2+ is abundant in living cells. The authors focused on the idea that pathogens respond to what they “feel” inside their cytoplasm, which can differ from the measured magnesium concentration in the host compartment. Using intracellular infection as the setting, the review connected host-driven stresses to bacterial magnesium homeostasis systems and showed how magnesium-related responses intersect with virulence control.

Who was reviewed?

Because this was a review, it did not study a single patient group. It reviewed host–pathogen evidence centered on mammalian macrophages and the macrophage resistance protein Slc11A1, alongside bacterial models that replicate within host vacuoles. The main pathogen framework was Salmonella enterica serovar Typhimurium, with supporting examples from other intracellular pathogens impacted by Slc11A1. The review also integrated bacterial genetic and regulatory studies that dissect magnesium transporters, stress sensors, and RNA leaders that report intracellular conditions.

What were the most important findings?

The review showed that magnesium limitation during infection is best understood as a regulated stress signal rather than a simple low-magnesium environment. Slc11A1 correlates with Salmonella experiencing a magnesium “starvation feeling,” and Salmonella needs the Mg2+ transporter MgtB to thrive in hosts with functional Slc11A1. The review clarified that PhoQ can sense low periplasmic Mg2+, but inside macrophages Salmonella mainly activates PhoQ through mildly acidic pH, which then drives PhoP-dependent virulence programs. A key microbiome-relevant concept is functional MMA at the pathway level: host pressures select for bacteria that can upregulate Mg2+ acquisition, tune transporter stability, and use RNA leaders to sense cytoplasmic Mg2+, ATP, and osmotic stress to sustain intracellular survival.

What are the greatest implications of this review?

This review reframes magnesium as a host-controlled ecological lever that can reshape pathogen behavior without directly changing bulk magnesium levels in a compartment. For clinicians translating microbiome science, the main implication is that infection risk and severity can hinge on host genes and host-cell conditions that alter what pathogens sense internally, not only on diet or serum minerals. It also supports anti-virulence thinking: targeting bacterial magnesium homeostasis, cytoplasmic sensing, or transporter stability may reduce intracellular pathogen fitness while avoiding some pressures that drive classic antibiotic resistance.