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The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range
The bacterial pathogen Staphylococcus pseudintermedius is involved in canine otitis externa and pyoderma as well as in surgical wound and urinary tract infections. Invasion of canine epithelial cells is promoted by S. pseudintermedius fibronectin (Fn)-binding proteins SpsD and SpsL through molecular...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343985/ https://www.ncbi.nlm.nih.gov/pubmed/32636242 http://dx.doi.org/10.1128/mBio.00371-20 |
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author | Viela, Felipe Mathelié-Guinlet, Marion Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. |
author_facet | Viela, Felipe Mathelié-Guinlet, Marion Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. |
author_sort | Viela, Felipe |
collection | PubMed |
description | The bacterial pathogen Staphylococcus pseudintermedius is involved in canine otitis externa and pyoderma as well as in surgical wound and urinary tract infections. Invasion of canine epithelial cells is promoted by S. pseudintermedius fibronectin (Fn)-binding proteins SpsD and SpsL through molecular interactions that are currently unknown. By means of single-molecule experiments, we discover that both adhesins have distinct molecular mechanisms for binding to Fn. We show that the SpsD-Fn interaction has a strength equivalent to that of a covalent bond (∼1.5 to 1.8 nN), which is an order of magnitude stronger than the binding force of classical receptor-ligand complexes. We suggest that this extreme mechanostability originates from the β-sheet organization of a tandem β-zipper. Upon binding to FnI modules, the intrinsically disordered binding sequences of SpsD would shift into an ordered structure by forming additional β-strands along triple peptide β-sheets in the Fn molecule. Dynamic force measurements reveal an unexpected behavior, i.e., that strong bonds are activated by mechanical tension as observed with catch bonds. By contrast, the SpsL-Fn interaction involves multiple weak bonds (∼0.2 nN) that rupture sequentially under force. Together with the recently described dock, lock, and latch complex, the ultrastrong interaction unraveled here is among the strongest noncovalent biological interaction measured to date. Our findings may find applications for the identification of inhibitory compounds to treat infections triggered by pathogens engaged in tandem β-zipper interactions. |
format | Online Article Text |
id | pubmed-7343985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-73439852020-07-10 The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range Viela, Felipe Mathelié-Guinlet, Marion Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. mBio Research Article The bacterial pathogen Staphylococcus pseudintermedius is involved in canine otitis externa and pyoderma as well as in surgical wound and urinary tract infections. Invasion of canine epithelial cells is promoted by S. pseudintermedius fibronectin (Fn)-binding proteins SpsD and SpsL through molecular interactions that are currently unknown. By means of single-molecule experiments, we discover that both adhesins have distinct molecular mechanisms for binding to Fn. We show that the SpsD-Fn interaction has a strength equivalent to that of a covalent bond (∼1.5 to 1.8 nN), which is an order of magnitude stronger than the binding force of classical receptor-ligand complexes. We suggest that this extreme mechanostability originates from the β-sheet organization of a tandem β-zipper. Upon binding to FnI modules, the intrinsically disordered binding sequences of SpsD would shift into an ordered structure by forming additional β-strands along triple peptide β-sheets in the Fn molecule. Dynamic force measurements reveal an unexpected behavior, i.e., that strong bonds are activated by mechanical tension as observed with catch bonds. By contrast, the SpsL-Fn interaction involves multiple weak bonds (∼0.2 nN) that rupture sequentially under force. Together with the recently described dock, lock, and latch complex, the ultrastrong interaction unraveled here is among the strongest noncovalent biological interaction measured to date. Our findings may find applications for the identification of inhibitory compounds to treat infections triggered by pathogens engaged in tandem β-zipper interactions. American Society for Microbiology 2020-07-07 /pmc/articles/PMC7343985/ /pubmed/32636242 http://dx.doi.org/10.1128/mBio.00371-20 Text en Copyright © 2020 Viela et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Viela, Felipe Mathelié-Guinlet, Marion Pietrocola, Giampiero Speziale, Pietro Dufrêne, Yves F. The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title | The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title_full | The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title_fullStr | The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title_full_unstemmed | The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title_short | The Molecular Complex between Staphylococcal Adhesin SpsD and Fibronectin Sustains Mechanical Forces in the Nanonewton Range |
title_sort | molecular complex between staphylococcal adhesin spsd and fibronectin sustains mechanical forces in the nanonewton range |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343985/ https://www.ncbi.nlm.nih.gov/pubmed/32636242 http://dx.doi.org/10.1128/mBio.00371-20 |
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