Zinc-dependent mechanical properties of Staphylococcus aureus biofilm-forming surface protein SasG

Research output: Contribution to journalArticle

Authors

  • Cécile Formosa-Dague
  • Pietro Speziale
  • Timothy J Foster
  • Joan Geoghegan
  • Yves F Dufrêne

Colleges, School and Institutes

External organisations

  • JMP Life Sciences, SAS Institute
  • University of Pavia
  • Trinity College Dublin

Abstract

Staphylococcus aureus surface protein SasG promotes cell-cell adhesion during the accumulation phase of biofilm formation, but the molecular basis of this interaction remains poorly understood. Here, we unravel the mechanical properties of SasG on the surface of living bacteria, that is, in its native cellular environment. Nanoscale multiparametric imaging of living bacteria reveals that Zn2+ strongly increases cell wall rigidity and activates the adhesive function of SasG. Single-cell force measurements show that SasG mediates cell-cell adhesion via specific Zn2+-dependent homophilic bonds between β-sheet-rich G5-E domains on neighboring cells. The force required to unfold individual domains is remarkably strong, up to ∼500 pN, thus explaining how SasG can withstand physiological shear forces. We also observe that SasG forms homophilic bonds with the structurally related accumulation-associated protein of Staphylococcus epidermidis, suggesting the possibility of multispecies biofilms during host colonization and infection. Collectively, our findings support a model in which zinc plays a dual role in activating cell-cell adhesion: adsorption of zinc ions to the bacterial cell surface increases cell wall cohesion and favors the projection of elongated SasG proteins away from the cell surface, thereby enabling zinc-dependent homophilic bonds between opposing cells. This work demonstrates an unexpected relationship between mechanics and adhesion in a staphylococcal surface protein, which may represent a general mechanism among bacterial pathogens for activating cell association.

Details

Original languageEnglish
Pages (from-to)410-415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number2
Publication statusPublished - 12 Jan 2016

Keywords

  • Bacterial Adhesion/drug effects, Bacterial Proteins/chemistry, Biofilms/drug effects, Biomechanical Phenomena/drug effects, Biophysical Phenomena/drug effects, Cell Membrane/drug effects, Cell Wall/drug effects, Membrane Proteins/chemistry, Microscopy, Atomic Force, Models, Biological, Protein Structure, Tertiary, Staphylococcus aureus/drug effects, Zinc/pharmacology