Genetic Regulation of Metal Ion Homeostasis in Staphylococcus aureus

The acquisition of metal ions and the proper maturation of holo-metalloproteins are essential processes for all organisms. However, metal ion homeostasis is a double-edged sword. A cytosolic accumulation of metal ions can lead to mismetallation of proteins and cell death. Therefore, maintenance of proper concentrations of intracellular metals is essential for cell fitness and pathogenesis. Staphylococcus aureus, like all bacterial pathogens, uses transcriptional metalloregulatory proteins to aid in the detection and the genetic response to changes in metal ion concentrations. Herein, we review the mechanisms by which S. aureus senses and responds to alterations in the levels of cellular zinc, iron, heme, and copper. The interplay between metal ion sensing and metal-dependent expression of virulence factors is also discussed.