부산대학교 도서관

Proline acquired via specific transporters can serve as a proteinogenic substrate, carbon and nitrogen source, or osmolyte. Previous reports have documented that Staphylococcus aureus, a major community and nosocomial pathogen, encodes at least four proline transporters, PutP, OpuC, OpuD, and ProP. A combination of genetic approaches and 3H-proline transport assays reveal that a previously unrecognized transporter, ProT, in addition to PutP, are the major proline transporters in S. aureus. Complementation experiments using constitutively expressed non-cognate promoters found that proline transport via OpuD, OpuC, and ProP is minimal. Both proline biosynthesis from arginine and proline transport via ProT are critical for growth when S. aureus is grown under conditions of high salinity. Further, proline transport mediated by ProT or PutP are required for growth in media with and without glucose, indicating both transporters function to acquire proline for proteinogenic purposes in addition to acquisition of proline as a carbon/nitrogen source. Lastly, inactivation of proT and putP resulted in a significant reduction (5 log10) of bacterial burden in murine skin-and-soft tissue infection and bacteremia models, suggesting that proline transport is required to establish a S. aureus infection. Author summary: The amino acid proline has multiple functions in the cell, including use as a basic building block for protein synthesis, carbon and nitrogen source, and compatible solute that protects the cells from osmotic stress. These studies reveal that the pathogen Staphylococcus aureus encodes two primary proline transporters, PutP and the newly described ProT, that are required for supporting growth in skin and soft tissue infections. Proline transport by either PutP or ProT is sufficient to support maximal growth when proline is utilized as a key carbon and nitrogen source, however, only ProT is required for growth in high salt conditions. [ABSTRACT FROM AUTHOR]