Acquisition of the phosphate transporter NptA enhances Staphylococcus aureus pathogenesis by improving phosphate uptake in divergent environments

During infection, pathogens must obtain all inorganic nutrients, such as phosphate, from the host. Despite the essentiality of phosphate for all forms of life, how Staphylococcus aureus obtains this nutrient during infection is unknown. Differing from Escherichia coli, the paradigm for bacterial phosphate acquisition, which has two inorganic phosphate (P_i) importers, genomic analysis suggested that S. aureus possesses three distinct P_i transporters: PstSCAB, PitA, and NptA. While pitA and nptA are expressed in phosphate-replete media, expression of all three transporters is induced by phosphate limitation. The loss of a single transporter did not affect S. aureus. However, disruption of any two systems significantly reduced P_i accumulation and growth in divergent environments. These findings indicate that PstSCAB, PitA, and NptA have overlapping but nonredundant functions, thus expanding the environments in which S. aureus can successfully obtain P_i. Consistent with this idea, in a systemic mouse model of disease, loss of any one transporter did not decrease staphylococcal virulence. However, loss of NptA in conjunction with either PstSCAB or PitA significantly reduced the ability of S. aureus to cause infection. These observations suggest that P_i acquisition via NptA is particularly important for the pathogenesis of S. aureus. While our analysis suggests that NptA homologs are widely distributed among bacteria, closely related less pathogenic staphylococcal species do not possess this importer. Altogether, these observations indicate that P_i uptake by S. aureus differs from established models and that acquisition of a third transporter enhances the ability of the bacterium to cause infection.