Staphylococcus aureus Preferentially Liberates Inorganic Phosphate from Organophosphates in Environments where This Nutrient Is Limiting

Phosphate is an essential nutrient that Staphylococcus aureus and other pathogens must acquire from the host during infection. While inorganic monophosphate (P i ) is the preferred source of this nutrient, bacteria can also obtain it from phosphate-containing organic molecules. The P i -responsive regulator PhoPR is necessary for S. aureus to cause infection, suggesting that P i is not freely available during infection and that this nutrient must be obtained from other sources. However, the organophosphates from which S. aureus can obtain phosphate are unknown. We evaluated the ability of 58 phosphorus-containing molecules to serve as phosphate sources for S. aureus . Forty-six of these compounds, including phosphorylated amino acids, sugars, and nucleotides, supported growth. Among the organophosphate sources was glycerol-3-phosphate (G3P), which is commonly found in the mammalian host. Differing from the model organism Escherichia coli , S. aureus does not import G3P intact to obtain P i . Instead, S. aureus relies on the phosphatase PhoB to release P i from G3P, which is subsequently imported by P i transporters. To determine if this strategy is used by S. aureus to extract phosphate from other phosphate sources, we assessed the ability of PhoB- and P i transporter-deficient strains to grow on the same library of phosphorus-containing molecules. Sixty percent of the substrates (28/46) relied on the PhoB/P i transporter pathway, and an additional 10/46 (22%) were PhoB independent but still required P i transport through the P i transporters. Cumulatively, these results suggest that in P i -limited environments, S. aureus preferentially generates P i from organophosphates and then relies on P i transporters to import this nutrient. IMPORTANCE For bacteria, the preferred form of the essential nutrient phosphate is inorganic monophosphate (P i ), but phosphate can also be extracted from a variety of phosphocompounds. Pathogens, including Staphylococcus aureus , experience P i limitation within the host, suggesting that the use of alternative phosphate sources is important during infection. However, the alternative phosphate sources that can be used by S. aureus and others remain largely unexplored. We screened a library of phosphorus-containing compounds for the ability to support growth as a phosphate source. S. aureus could use a variety of phosphocompounds, including nucleotides, phosphosugars, and phosphoamino acids. Subsequent genetic analysis determined that a majority of these alternative phosphate sources are first processed extracellularly to liberate P i , which is then imported through P i transporters.