title: Sticky Matrix: Adhesion Mechanism of the Staphylococcal Polysaccharide Intercellular Adhesin.
abstract: The development of bacterial biofilms on surfaces leads to hospital-acquired infections that are difficult to fight. In Staphylococci, the cationic polysaccharide intercellular adhesin (PIA) forms an extracellular matrix that connects the cells together during biofilm formation, but the molecular forces involved are unknown. Here, we use advanced force nanoscopy techniques to unravel the mechanism of PIA-mediated adhesion in a clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strain. Nanoscale multiparametric imaging of the structure, adhesion, and elasticity of bacteria expressing PIA shows that the cells are surrounded by a soft and adhesive matrix of extracellular polymers. Cell surface softness and adhesion are dramatically reduced in mutant cells deficient for the synthesis of PIA or under unfavorable growth conditions. Single-cell force spectroscopy demonstrates that PIA promotes cell-cell adhesion via the multivalent electrostatic interaction with polyanionic teichoic acids on the S. aureus cell surface. This binding mechanism rationalizes, at the nanoscale, the well-known ability of PIA to strengthen intercellular adhesion in staphylococcal biofilms. Force nanoscopy offers promising prospects for understanding the fundamental forces in antibiotic-resistant biofilms and for designing anti-adhesion compounds targeting matrix polymers.
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain , Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Formosa-Dague
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain , Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Feuillie
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain , Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Beaussart
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain , Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Derclaye
authors.affiliation: Department of Molecular Microbiology, VIB,,  KU Leuven, 3000 Leuven, Belgium|Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, 3000 Leuven, Belgium
authors.forename: Soňa
authors.initials: S
authors.lastname: Kucharíková
authors.affiliation: Group of Microbial Communities and Disease, Navarrabiomed-FMS, UPNA, IdiSNA, 31008 Navarra, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lasa
authors.affiliation: Department of Molecular Microbiology, VIB,,  KU Leuven, 3000 Leuven, Belgium|Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, 3000 Leuven, Belgium
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dijck
authors.affiliation: Institute of Life Sciences, Université catholique de Louvain , Croix du Sud, 4-5, bte L7.07.06., B-1348 Louvain-la-Neuve, Belgium.|Walloon Excellence in Life sciences and Biotechnology (WELBIO), 1300 Wavre, Belgium.
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
mesh_terms: D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D006801:Humans; D018625:Microscopy, Atomic Force; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000166:cytology / Q000502:physiology*
chemical_list: D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin
keywords: Staphylococcus aureus; adhesion forces; atomic force microscopy; biofilm matrix; polysaccharide intercellular adhesin