title: Protein A-mediated multicellular behavior in Staphylococcus aureus.
abstract: The capacity of Staphylococcus aureus to form biofilms on host tissues and implanted medical devices is one of the major virulence traits underlying persistent and chronic infections. The matrix in which S. aureus cells are encased in a biofilm often consists of the polysaccharide intercellular adhesin (PIA) or poly-N-acetyl glucosamine (PNAG). However, surface proteins capable of promoting biofilm development in the absence of PIA/PNAG exopolysaccharide have been described. Here, we used two-dimensional nano-liquid chromatography and mass spectrometry to investigate the composition of a proteinaceous biofilm matrix and identified protein A (spa) as an essential component of the biofilm; protein A induced bacterial aggregation in liquid medium and biofilm formation under standing and flow conditions. Exogenous addition of synthetic protein A or supernatants containing secreted protein A to growth media induced biofilm development, indicating that protein A can promote biofilm development without being covalently anchored to the cell wall. Protein A-mediated biofilm formation was completely inhibited in a dose-dependent manner by addition of serum, purified immunoglobulin G, or anti-protein A-specific antibodies. A murine model of subcutaneous catheter infection unveiled a significant role for protein A in the development of biofilm-associated infections, as the amount of protein A-deficient bacteria recovered from the catheter was significantly lower than that of wild-type bacteria when both strains were used to coinfect the implanted medical device. Our results suggest a novel role for protein A complementary to its known capacity to interact with multiple immunologically important eukaryotic receptors.
authors.affiliation: Instituto de Agrobiotecnología, Universidad Pública de Navarra, Pamplona 31006, Spain.
authors.forename: Nekane
authors.initials: N
authors.lastname: Merino
authors.forename: Alejandro
authors.initials: A
authors.lastname: Toledo-Arana
authors.forename: Marta
authors.initials: M
authors.lastname: Vergara-Irigaray
authors.forename: Jaione
authors.initials: J
authors.lastname: Valle
authors.forename: Cristina
authors.initials: C
authors.lastname: Solano
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Lopez
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.forename: José R
authors.initials: JR
authors.lastname: Penadés
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lasa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects / Q000235:genetics; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D015153:Blotting, Western; D055499:Catheter-Related Infections / Q000382:microbiology; D002853:Chromatography, Liquid; D004586:Electrophoresis; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D044967:Serum; D013203:Staphylococcal Infections / Q000382:microbiology; D013205:Staphylococcal Protein A / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053719:Tandem Mass Spectrometry
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A