title: The Staphylococcus aureus Membrane Protein SA2056 Interacts with Peptidoglycan Synthesis Enzymes.
abstract: The yet uncharacterized membrane protein SA2056 belongs to the ubiquitous RND (Resistance-Nodulation-cell Division) family of transmembrane efflux transporters. The sa2056 gene is located downstream of femX, the gene encoding the essential, non-ribosomal peptidyl-transferase adding the first glycine in the staphylococcal cell wall pentaglycine interpeptide. Due to its proximity to and weak co-transcription with femX, we assumed that sa2056 may somehow be involved in peptidoglycan synthesis. Specific antibodies against SA2056 showed that this protein is expressed during growth and present in the membrane fraction of cell preparations. Using a bacterial two hybrid system, SA2056 was shown to interact (i) with itself, (ii) with FemB, which adds glycines 4 and 5 to the peptidoglycan interpeptide and (iii) with the essential penicillin binding proteins, PBP1 and PBP2, required for cell division and incorporation of the peptidoglycan into the cell wall. Unexpectedly, deletion of sa2056 led to no phenotype regarding growth, antibiotic resistances or cell morphology; nor did sa2056 deletion in combination with femB inactivation alter b-lactam and lysostaphin sensitivity and resistance, respectively, pointing to possible redundancy in the cell wall synthesis pathway. These results suggest an accessory role of SA2056 in S. aureus peptidoglycan synthesis, broadening the range of biological functions of RND proteins.
authors.affiliation: Institute of Medical Microbiology, University of Zurich / Gloriastrasse 32, 8006 Zurich, Switzerland. chantalquiblier@access.uzh.ch.
authors.forename: Chantal
authors.initials: C
authors.lastname: Quiblier
authors.affiliation: Centre of Quality Control in Microbiology / ul. Chelmska 30/34, 00-725 Warsaw, Poland. luczakowa@interia.pl.|AMSolutions, ul. Debowa 32, 05-123 Chotomow, Poland. luczakowa@interia.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Luczak-Kadlubowska
authors.affiliation: Institute of Medical Microbiology, University of Zurich / Gloriastrasse 32, 8006 Zurich, Switzerland. esther.holdener@alumni.ethz.ch.
authors.forename: Esther
authors.initials: E
authors.lastname: Holdener
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn / Meckenheimer Allee 168, 53115 Bonn, Germany. dalborn@uni-bonn.de.
authors.forename: Daniela
authors.initials: D
authors.lastname: Alborn
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn / Meckenheimer Allee 168, 53115 Bonn, Germany. tanja@mibi03.meb.uni-bonn.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn / Meckenheimer Allee 168, 53115 Bonn, Germany. iwiedemann@medpharmaservice.de.
authors.forename: Imke
authors.initials: I
authors.lastname: Wiedemann
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa / Av. Da Républica (EAN), 2781-901 Oeiras, Portugal. mgpinho@itqb.unl.pt.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Pinho
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn / Meckenheimer Allee 168, 53115 Bonn, Germany. sahl@mibi03.meb.uni-bonn.de.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.affiliation: Institute of Medical Microbiology, University of Zurich / Gloriastrasse 32, 8006 Zurich, Switzerland. susanne_elisabeth.rohrer@alumni.ethz.ch.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rohrer
authors.affiliation: Institute of Medical Microbiology, University of Zurich / Gloriastrasse 32, 8006 Zurich, Switzerland. bberger@imm.uzh.ch.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Berger-Bächi
authors.affiliation: Institute of Medical Microbiology, University of Zurich / Gloriastrasse 32, 8006 Zurich, Switzerland. msenn@imm.uzh.ch.
authors.forename: Maria Magdalena
authors.initials: MM
authors.lastname: Senn
keywords: FemABX; PBP; RND protein; Staphylococcus aureus; bacterial two-hybrid system; peptidoglycan