@article{67398db20f134bafbb38468bca9e8532,
title = "The staphylococcus aureus chaperone PrsA is a new auxiliary factor of oxacillin resistance affecting penicillin-binding protein 2A",
abstract = "Expression of the methicillin-resistant S. aureus (MRSA) phenotype results from the expression of the extra penicillin-binding protein 2A (PBP2A), which is encoded by mecA and acquired horizontally on part of the SCCmec cassette. PBP2A can catalyze DD-transpeptidation of peptidoglycan (PG) because of its low affinity for β-lactam antibiotics and can functionally cooperate with the PBP2 transglycosylase in the biosynthesis of PG. Here, we focus upon the role of the membrane-bound PrsA foldase protein as a regulator of β-lactam resistance expression. Deletion of prsA altered oxacillin resistance in three different SCCmec backgrounds and, more importantly, caused a decrease in PBP2A membrane amounts without affecting mecA mRNA levels. The N- and C-terminal domains of PrsA were found to be critical features for PBP2A protein membrane levels and oxacillin resistance. We propose that PrsA has a role in posttranscriptional maturation of PBP2A, possibly in the export and/or folding of newly synthesized PBP2A. This additional level of control in the expression of the mecA-dependent MRSA phenotype constitutes an opportunity to expand the strategies to design anti-infective agents.",
author = "Ambre Jousselin and Caroline Manzano and Alexandra Biette and Patricia Reed and Pinho, {Mariana G.} and Rosato, {Adriana E.} and Kelley, {William L.} and Adriana Renzoni",
note = "Funding Information: This study was supported by the Swiss National Science Foundation grants (A.R., 310030-149762; W.L.K., 10030-146540), National Institutes of Health grant (A.R., NIH-R56AI102503-01A1) and by the European Research Council through grant (M.G.P., ERC-2012-StG-310987). A.J. is supported by the FNS through project funding P300P3_155346. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. We are very grateful to Vesa Kontinen and Liz Harry for, respectively, sharing PrsA and FtsZ antibodies. HHS| National Institutes of Health (NIH) provided funding to Adriana E. Rosato under grant number NIH-R56AI102503-01A1. EC | European Research Council (ERC) provided funding to Mariana G. Pinho under grant number ERC-2012-StG-310987. Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (SNF) provided funding to Adriana Renzoni under grant number 310030-149762. Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (SNF) provided funding to William L. Kelley under grant number 10030- 146540. Publisher Copyright: Copyright {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",
year = "2016",
month = mar,
doi = "10.1128/AAC.02333-15",
language = "English (US)",
volume = "60",
pages = "1656--1666",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "3",
}