Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC.
Staphylococcus aureusforms biofilms on indwelling medical devices using a variety of cell-surface proteins. There is growing evidence that specific homophilic interactions between these proteins represent an important mechanism of cell accumulation during biofilm formation, but the underlying molecular mechanisms are still not well-understood. Here we report the direct measurement of homophilic binding forces by the serine-aspartate repeat protein SdrC and their inhibition by a peptide. Using single-cell and single-molecule force measurements, we find that SdrC is engaged in low-affinity homophilic bonds that promote cell-cell adhesion. Low-affinity intercellular adhesion may play a role in favoring biofilm dynamics. We show that SdrC also mediates strong cellular interactions with hydrophobic surfaces, which are likely to be involved in the initial attachment to biomaterials, the first stage of biofilm formation. Furthermore, we demonstrate that a peptide derived from β-neurexin is a powerful competitive inhibitor capable of efficiently blocking surface attachment, homophilic adhesion, and biofilm accumulation. Molecular modeling suggests that this blocking activity may originate from binding of the peptide to a sequence of SdrC involved in homophilic interactions. Our study opens up avenues for understanding the role of homophilic interactions in staphylococcal adhesion, and for the design of new molecules to prevent biofilm formation during infection.
Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Cécile
C
Feuillie
Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Cécile
C
Formosa-Dague
Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
Leanne M C
LM
Hays
Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Ophélie
O
Vervaeck
Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Sylvie
S
Derclaye
Molecular and Cellular Therapeutics, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Marian P
MP
Brennan
Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
Timothy J
TJ
Foster
Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland; geoghegj@tcd.ie yves.dufrene@uclouvain.be.
Joan A
JA
Geoghegan
Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium; geoghegj@tcd.ie yves.dufrene@uclouvain.be.|Walloon Excellence in Life Sciences and Biotechnology (WELBIO), 1300 Wavre, Belgium.
Yves F
YF
Dufrêne
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018441:Biofilms; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D059010:Single-Cell Analysis; D013211:Staphylococcus aureus / Q000502:physiology*
D001426:Bacterial Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; C118508:SdrC protein, Staphylococcus aureus
SdrC; Staphylococcus aureus; adhesion; biofilms; inhibition