Acquisition of the Phosphate Transporter NptA Enhances Staphylococcus aureus Pathogenesis by Improving Phosphate Uptake in Divergent Environments

Abstract

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 obtains this nutrient during infection is unknown. Differing from, the paradigm for bacterial phosphate acquisition, which has two inorganic phosphate (P) importers, genomic analysis suggested that possesses three distinct P transporters: PstSCAB, PitA, and NptA. While and 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 However, disruption of any two systems significantly reduced P 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 can successfully obtain P 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 to cause infection. These observations suggest that P acquisition via NptA is particularly important for the pathogenesis of 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 uptake by differs from established models and that acquisition of a third transporter enhances the ability of the bacterium to cause infection.

Synergy between Nutritional Immunity and Independent Host Defenses Contributes to the Importance of the MntABC Manganese Transporter during Staphylococcus aureus Infection

“…PitA is constitutively expressed, while PstSCAB is expressed in response to nutrient limitation. Forcing S. aureus to rely on PstSCAB in phosphate-replete medium results in a reduced growth rate (81). Hence, it is not unreasonable to speculate that, similarly to PitA, MntH is retained because of its greater energy efficiency for the pathogen.…”

PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

“…including Escherichia coli and other Enterobacteriaceae, Vibrio cholerae, Mycobacterium tuberculosis, and Streptococcus pneumoniae (11)(12)(13)(14)(15)(16)(17)(18). S. aureus encodes three P i transporters that are important for growth in distinct environments and differentially contribute to staphylococcal pathogenesis ( Fig.…”

“…S. aureus encodes three P i transporters that are important for growth in distinct environments and differentially contribute to staphylococcal pathogenesis ( Fig. 1) (18). Two of these P i transporters, PstSCAB and PitA, are similar to those found in E. coli, the primary model for the study of bacterial P i acquisition.…”

A metabolomic investigation into the temperature‐dependent virulence of Pseudomonas plecoglossicida from large yellow croaker (Pseudosciaena crocea)

“…Invading microbes have to acquire Phosphoric acid from their host. Phosphoric acid transporters were observed in pathogens, including Salmonella Typhimurium , pathogenic Escherichia coli , Enterobacteriaceae , Mycobacterium tuberculosis , Vibrio cholerae , Streptococcus pneumonia and Staphylococcus aureus and closely related to their pathogenicity (Burall et al, ; Darwin & Miller, ; Hava & Camilli, ; Kelliher et al, ; Lamarche, Wanner, Crépin, & Harel, ; Lathem, Crosby, Miller, & Goldman, ; Merrell, Hava, & Camilli, ; Peirs et al, ; Valdivia & Falkow, ).…”

“…For most bacteria, inorganic Phosphoric acid (Pi) is the preferred source of Phosphoric acid. Three distinct classes of Pi importers were observed in bacteria: PitA, PstSCAB system and NptA (Kelliher et al, ). Genomic analysis suggested that P. plecoglossicida possesses all of these three distinct Pi transporters.…”