Genetic screens reveal novel major and minor players in magnesium homeostasis of Staphylococcus aureus.

Author summary Magnesium is the most abundant metal ion in cells, yet to grow they still need to maintain its concentration within acceptable parameters relying on transporters capable of importing or exporting magnesium. This is essential to allow cells to strive in varying conditions, whether the environment is rich in magnesium, such as bones or kidneys, or poor in magnesium. Here, using various genetics screens, we identified the main transporters involved in this process in the opportunistic pathogen Staphylococcus aureus. Surprisingly, magnesium homeostasis had never been properly studied in this bacterium, while it is key in allowing S. aureus to colonize many different organs. We show that import and export are two independent systems. Two transporters, of two different well characterized families, MgtE and CorA, are necessary for import. Export of magnesium is mediated by MpfA, a distant homolog of a mammalian CNNM family of magnesium transport mediators. Magnesium is one of the most abundant metal ions in living cells. Very specific and devoted transporters have evolved for transporting Mg2+ ions across the membrane and maintain magnesium homeostasis. Using genetic screens, we were able to identify the main players in magnesium homeostasis in the opportunistic pathogen Staphylococcus aureus. Here, we show that import of magnesium relies on the redundant activity of either CorA2 or MgtE since in absence of these two importers, bacteria require increased amounts of magnesium in the medium. A third CorA-like importer seems to play a minor role, at least under laboratory conditions. For export of magnesium, we identified two proteins, MpfA and MpfB. MpfA, is the main actor since it is essential for growth in high magnesium concentrations. We show that gain of function mutations or overexpression of the minor factor, MpfB, which is part of a sigmaB controlled stress response regulon, can compensate for the absence of MpfA.