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Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
Post-weaning diarrhea and edema disease caused by F18 fimbriated E. coli are important diseases in newly weaned piglets and lead to severe production losses in farming industry. Protective treatments against these infections have thus far limited efficacy. In this study we generated nanobodies direc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263667/ https://www.ncbi.nlm.nih.gov/pubmed/25502211 http://dx.doi.org/10.1371/journal.pone.0114691 |
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author | Moonens, Kristof De Kerpel, Maia Coddens, Annelies Cox, Eric Pardon, Els Remaut, Han De Greve, Henri |
author_facet | Moonens, Kristof De Kerpel, Maia Coddens, Annelies Cox, Eric Pardon, Els Remaut, Han De Greve, Henri |
author_sort | Moonens, Kristof |
collection | PubMed |
description | Post-weaning diarrhea and edema disease caused by F18 fimbriated E. coli are important diseases in newly weaned piglets and lead to severe production losses in farming industry. Protective treatments against these infections have thus far limited efficacy. In this study we generated nanobodies directed against the lectin domain of the F18 fimbrial adhesin FedF and showed in an in vitro adherence assay that four unique nanobodies inhibit the attachment of F18 fimbriated E. coli bacteria to piglet enterocytes. Crystallization of the FedF lectin domain with the most potent inhibitory nanobodies revealed their mechanism of action. These either competed with the binding of the blood group antigen receptor on the FedF surface or induced a conformational change in which the CDR3 region of the nanobody displaces the D″-E loop adjacent to the binding site. This D″-E loop was previously shown to be required for the interaction between F18 fimbriated bacteria and blood group antigen receptors in a membrane context. This work demonstrates the feasibility of inhibiting the attachment of fimbriated pathogens by employing nanobodies directed against the adhesin domain. |
format | Online Article Text |
id | pubmed-4263667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42636672014-12-19 Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli Moonens, Kristof De Kerpel, Maia Coddens, Annelies Cox, Eric Pardon, Els Remaut, Han De Greve, Henri PLoS One Research Article Post-weaning diarrhea and edema disease caused by F18 fimbriated E. coli are important diseases in newly weaned piglets and lead to severe production losses in farming industry. Protective treatments against these infections have thus far limited efficacy. In this study we generated nanobodies directed against the lectin domain of the F18 fimbrial adhesin FedF and showed in an in vitro adherence assay that four unique nanobodies inhibit the attachment of F18 fimbriated E. coli bacteria to piglet enterocytes. Crystallization of the FedF lectin domain with the most potent inhibitory nanobodies revealed their mechanism of action. These either competed with the binding of the blood group antigen receptor on the FedF surface or induced a conformational change in which the CDR3 region of the nanobody displaces the D″-E loop adjacent to the binding site. This D″-E loop was previously shown to be required for the interaction between F18 fimbriated bacteria and blood group antigen receptors in a membrane context. This work demonstrates the feasibility of inhibiting the attachment of fimbriated pathogens by employing nanobodies directed against the adhesin domain. Public Library of Science 2014-12-11 /pmc/articles/PMC4263667/ /pubmed/25502211 http://dx.doi.org/10.1371/journal.pone.0114691 Text en © 2014 Moonens et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Moonens, Kristof De Kerpel, Maia Coddens, Annelies Cox, Eric Pardon, Els Remaut, Han De Greve, Henri Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli |
title | Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
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title_full | Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
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title_fullStr | Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
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title_full_unstemmed | Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
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title_short | Nanobody Mediated Inhibition of Attachment of F18 Fimbriae Expressing Escherichia coli
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title_sort | nanobody mediated inhibition of attachment of f18 fimbriae expressing escherichia coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263667/ https://www.ncbi.nlm.nih.gov/pubmed/25502211 http://dx.doi.org/10.1371/journal.pone.0114691 |
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