Proline transporters ProT and PutP are required for Staphylococcus aureus infection.

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....

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Main Authors: McKenzie K Lehman, Natalie A Sturd, Fareha Razvi, Dianne L Wellems, Steven D Carson, Paul D Fey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1011098
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author McKenzie K Lehman
Natalie A Sturd
Fareha Razvi
Dianne L Wellems
Steven D Carson
Paul D Fey
author_facet McKenzie K Lehman
Natalie A Sturd
Fareha Razvi
Dianne L Wellems
Steven D Carson
Paul D Fey
author_sort McKenzie K Lehman
collection DOAJ
description 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.
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spelling doaj.art-eb0ba8c5f301478691573e1d92982e832023-04-21T05:31:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-01-01191e101109810.1371/journal.ppat.1011098Proline transporters ProT and PutP are required for Staphylococcus aureus infection.McKenzie K LehmanNatalie A SturdFareha RazviDianne L WellemsSteven D CarsonPaul D FeyProline 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.https://doi.org/10.1371/journal.ppat.1011098
spellingShingle McKenzie K Lehman
Natalie A Sturd
Fareha Razvi
Dianne L Wellems
Steven D Carson
Paul D Fey
Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
PLoS Pathogens
title Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
title_full Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
title_fullStr Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
title_full_unstemmed Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
title_short Proline transporters ProT and PutP are required for Staphylococcus aureus infection.
title_sort proline transporters prot and putp are required for staphylococcus aureus infection
url https://doi.org/10.1371/journal.ppat.1011098
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