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.
authors.affiliation: 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.
authors.forename: Ambre
authors.initials: A
authors.lastname: Jousselin
authors.affiliation: Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Manzano
authors.affiliation: Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Biette
authors.affiliation: Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Patricia
authors.initials: P
authors.lastname: Reed
authors.affiliation: Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Pinho
authors.affiliation: Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Adriana E
authors.initials: AE
authors.lastname: Rosato
authors.affiliation: Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland.
authors.forename: William L
authors.initials: WL
authors.lastname: Kelley
authors.affiliation: Infectious Diseases Service, University Hospital and Medical School of Geneva, Geneva, Switzerland adriana.renzoni@hcuge.ch.
authors.forename: Adriana
authors.initials: A
authors.lastname: Renzoni
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology; D046915:Penicillin-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D010457:Peptidoglycan / Q000378:metabolism; D046928:Peptidoglycan Glycosyltransferase / Q000378:metabolism; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics; D018440:beta-Lactam Resistance / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D012333:RNA, Messenger; C487789:mecA protein, Staphylococcus aureus; C082160:prsA protein, bacteria; D046928:Peptidoglycan Glycosyltransferase; D010068:Oxacillin