An Essential Factor for High Mg2+ Tolerance of Staphylococcus aureus Original paper

What was studied?

This study investigated why Staphylococcus aureus tolerates unusually high external magnesium and which bacterial factor protects it from magnesium toxicity. The authors focused on the gene SA0657, discovered during a suppressor screen that restored growth of a slow-growing ΔcshB mutant on serum-like media. They then tested whether SA0657 helps the cell survive high Mg2+ by controlling intracellular magnesium balance, and they mapped which protein features are essential for this protective role.

Who was studied?

The study examined bacterial strains, not patients. The authors used Staphylococcus aureus laboratory strains with targeted deletions and reconstructed point mutations in SA0657, including multiple independent loss-of-function suppressor mutants. They compared wild-type bacteria to ΔSA0657 strains and to strains carrying a key SA0657 point mutation that altered a conserved residue in a predicted Mg2+-sensing domain. They also performed complementation with plasmids expressing the wild-type or mutant SA0657 allele to confirm causality.

What were the most important findings?

The authors identified SA0657 as a required factor for high Mg2+ tolerance and renamed it MpfA (Magnesium Protection Factor A). Loss of MpfA made S. aureus dramatically sensitive to magnesium: in defined RPMI medium, adding only about 10 mM Mg2+ was enough to inhibit growth, while wild-type bacteria normally tolerate far higher Mg2+ levels. The study showed that many independent suppressor mutations truncated SA0657, and two distinct suppressors hit the same conserved glycine (Gly326) inside a CBS-domain pair, establishing this residue as critical for function. MpfA mutants also showed altered responses to other divalent cations (notably cobalt and manganese), consistent with a central role in divalent-ion handling rather than a nonspecific salt effect.

What are the greatest implications of this study?

This work strengthens the idea that pathogens actively manage magnesium stress, not only by importing Mg2+ when it is scarce but also by preventing toxic accumulation when Mg2+ is abundant. For clinicians, the practical message is that magnesium availability can shape pathogen physiology and stress tolerance, which may influence survival in distinct host niches and during inflammation. Mechanistically, the study proposes MpfA as an Mg2+ exporter or an essential component of export, filling an important gap because bacterial Mg2+ export remains poorly defined. It also links MpfA-like proteins to the broader CorB/CNNM family, reinforcing that conserved Mg2+-sensing modules can control transport behaviors across species.