The staphylococcus aureus chaperone PrsA is a new auxiliary factor of oxacillin resistance affecting penicillin-binding protein 2A

Ambre Jousselin, Caroline Manzano, Alexandra Biette, Patricia Reed, Mariana G. Pinho, Adriana E. Rosato, William L. Kelley, Adriana Renzoni

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1656-1666
Number of pages11
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number3
DOIs
StatePublished - Mar 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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