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Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein

We have previously described a native human monoclonal antibody, TRL1068, that disrupts bacterial biofilms by extracting from the biofilm matrix key scaffolding proteins in the DNABII family, which are present in both gram positive and gram negative bacterial species. The antibiotic resistant sessil...

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Autores principales: Ryser, Stefan, Tenorio, Edgar, Estellés, Angeles, Kauvar, Lawrence M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615618/
https://www.ncbi.nlm.nih.gov/pubmed/31287831
http://dx.doi.org/10.1371/journal.pone.0219256
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author Ryser, Stefan
Tenorio, Edgar
Estellés, Angeles
Kauvar, Lawrence M.
author_facet Ryser, Stefan
Tenorio, Edgar
Estellés, Angeles
Kauvar, Lawrence M.
author_sort Ryser, Stefan
collection PubMed
description We have previously described a native human monoclonal antibody, TRL1068, that disrupts bacterial biofilms by extracting from the biofilm matrix key scaffolding proteins in the DNABII family, which are present in both gram positive and gram negative bacterial species. The antibiotic resistant sessile bacteria released from the biofilm then revert to the antibiotic sensitive planktonic state. Qualitative resensitization to antibiotics has been demonstrated in three rodent models of acute infections. We report here the surprising discovery that antibodies against the target family were found in all twenty healthy humans surveyed, albeit at a low level requiring a sensitive single B-cell assay for detection. We have cloned 21 such antibodies. Aside from TRL1068, only one (TRL1330) has all the biochemical properties believed necessary for pharmacological efficacy (broad spectrum epitope specificity and high affinity). We suggest that the other anti-DNABII antibodies, while not necessarily curative, reflect an immune response at some point in the donor’s history to these components of biofilms. Such an immune response could reflect exposure to bacterial reservoirs that have been previously described in chronic non-healing wounds, periodontal disease, chronic obstructive pulmonary disease, colorectal cancer, rheumatoid arthritis, and atherosclerotic artery explants. The detection of anti-DNABII antibodies in all twenty surveyed donors with no active infection suggests that bacterial biofilm reservoirs may be present periodically in most healthy individuals. Biofilms routinely shed bacteria, creating a continuous low level inflammatory stimulus. Since chronic subclinical inflammation is thought to contribute to most aging-related diseases, suppression of bacterial biofilm has potential value in delaying age-related pathology.
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spelling pubmed-66156182019-07-25 Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein Ryser, Stefan Tenorio, Edgar Estellés, Angeles Kauvar, Lawrence M. PLoS One Research Article We have previously described a native human monoclonal antibody, TRL1068, that disrupts bacterial biofilms by extracting from the biofilm matrix key scaffolding proteins in the DNABII family, which are present in both gram positive and gram negative bacterial species. The antibiotic resistant sessile bacteria released from the biofilm then revert to the antibiotic sensitive planktonic state. Qualitative resensitization to antibiotics has been demonstrated in three rodent models of acute infections. We report here the surprising discovery that antibodies against the target family were found in all twenty healthy humans surveyed, albeit at a low level requiring a sensitive single B-cell assay for detection. We have cloned 21 such antibodies. Aside from TRL1068, only one (TRL1330) has all the biochemical properties believed necessary for pharmacological efficacy (broad spectrum epitope specificity and high affinity). We suggest that the other anti-DNABII antibodies, while not necessarily curative, reflect an immune response at some point in the donor’s history to these components of biofilms. Such an immune response could reflect exposure to bacterial reservoirs that have been previously described in chronic non-healing wounds, periodontal disease, chronic obstructive pulmonary disease, colorectal cancer, rheumatoid arthritis, and atherosclerotic artery explants. The detection of anti-DNABII antibodies in all twenty surveyed donors with no active infection suggests that bacterial biofilm reservoirs may be present periodically in most healthy individuals. Biofilms routinely shed bacteria, creating a continuous low level inflammatory stimulus. Since chronic subclinical inflammation is thought to contribute to most aging-related diseases, suppression of bacterial biofilm has potential value in delaying age-related pathology. Public Library of Science 2019-07-09 /pmc/articles/PMC6615618/ /pubmed/31287831 http://dx.doi.org/10.1371/journal.pone.0219256 Text en © 2019 Ryser 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ryser, Stefan
Tenorio, Edgar
Estellés, Angeles
Kauvar, Lawrence M.
Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title_full Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title_fullStr Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title_full_unstemmed Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title_short Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
title_sort human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615618/
https://www.ncbi.nlm.nih.gov/pubmed/31287831
http://dx.doi.org/10.1371/journal.pone.0219256
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