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dc.contributor.authorFOSTER, TIMOTHYen
dc.date.accessioned2017-01-17T12:25:21Z
dc.date.available2017-01-17T12:25:21Z
dc.date.issued2016en
dc.date.submitted2016en
dc.identifier.citationHerman-Bausier P, Valotteau C, Pietrocola G, Rindi S, Alsteens D, Foster T.J, Speziale P, Dufrêne Y.F, Mechanical strength and inhibition of the Staphylococcus aureus collagen-binding protein Cna, mBio, 7, 5, 2016, e01529-16en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/78773
dc.description.abstractThe bacterial pathogen Staphylococcus aureus expresses a variety of cell surface adhesion proteins that bind to host extracellular matrix proteins. Among these, the collagen (Cn)-binding protein Cna plays important roles in bacterium-host adherence and in immune evasion. While it is well established that the A region of Cna mediates ligand binding, whether the repetitive B region has a dedicated function is not known. Here, we report the direct measurement of the mechanical strength of Cna-Cn bonds on living bacteria, and we quantify the antiadhesion activity of monoclonal antibodies (MAbs) targeting this interaction. We demonstrate that the strength of Cna-Cn bonds in vivo is very strong (~1.2 nN), consistent with the high-affinity “collagen hug” mechanism. The B region is required for strong ligand binding and has been found to function as a spring capable of sustaining high forces. This previously undescribed mechanical response of the B region is of biological significance as it provides a means to project the A region away from the bacterial surface and to maintain bacterial adhesion under conditions of high forces. We further quantified the antiadhesion activity of MAbs raised against the A region of Cna directly on living bacteria without the need for labeling or purification. Some MAbs are more efficient in blocking single-cell adhesion, suggesting that they act as competitive inhibitors that bind Cna residues directly involved in ligand binding. This report highlights the role of protein mechanics in activating the function of staphylococcal adhesion proteins and emphasizes the potential of antibodies to prevent staphylococcal adhesion and biofilm formation. IMPORTANCE: Cna is a collagen (Cn)-binding protein from Staphylococcus aureus that is involved in pathogenesis. Currently, we know little about the functional role of the repetitive B region of the protein. Here, we unravel the mechanical strength of Cna in living bacteria. We show that single Cna-Cn bonds are very strong, reflecting high-affinity binding by the collagen hug mechanism. We discovered that the B region behaves as a nanospring capable of sustaining high forces. This unanticipated mechanical response, not previously described for any staphylococcal adhesin, favors a model in which the B region has a mechanical function that is essential for strong ligand binding. Finally, we assess the antiadhesion activity of monoclonal antibodies against Cna, suggesting that they could be used to inhibit S. aureus adhesion. © 2016 Herman-Bausier et al.en
dc.description.sponsorshipEuropean Research Council ERC WELBIO-CR-2015A-05 Fonds De La Recherche Scientifique - FNRS FNRSen
dc.format.extente01529-16en
dc.relation.ispartofseriesmBioen
dc.relation.ispartofseries7en
dc.relation.ispartofseries5en
dc.rightsYen
dc.subjectStaphylococcus aureusen
dc.subject.lcshStaphylococcus aureusen
dc.titleMechanical strength and inhibition of the Staphylococcus aureus collagen-binding protein Cnaen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/tfosteren
dc.identifier.rssinternalid138498en
dc.identifier.doihttp://dx.doi.org/10.1128/mBio.01529-16en
dc.rights.ecaccessrightsopenAccess
dc.identifier.rssurihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84994477687&doi=10.1128%2fmBio.01529-16&partnerID=40&md5=702b1d7f2349936f740f054d03c0731aen


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