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Antimicrob Agents Chemother. 2015 Dec 28;60(3):1656-66. doi: 10.1128/AAC.02333-15.

The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A.

Author information

1
Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
2
Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland.
3
Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
4
Houston Methodist Research Institute, Houston, Texas, USA.
5
Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland adriana.renzoni@hcuge.ch.

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.

PMID:
26711778
PMCID:
PMC4775990
DOI:
10.1128/AAC.02333-15
[Indexed for MEDLINE]
Free PMC Article

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