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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Main Authors: Stefan Ryser, Edgar Tenorio, Angeles Estellés, Lawrence M Kauvar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0219256
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spelling doaj-f3d9543f9995425d8634ecb15aa67f652021-03-04T11:22:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021925610.1371/journal.pone.0219256Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein.Stefan RyserEdgar TenorioAngeles EstellésLawrence M KauvarWe 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.https://doi.org/10.1371/journal.pone.0219256
collection DOAJ
language English
format Article
sources DOAJ
author Stefan Ryser
Edgar Tenorio
Angeles Estellés
Lawrence M Kauvar
spellingShingle Stefan Ryser
Edgar Tenorio
Angeles Estellés
Lawrence M Kauvar
Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein.
PLoS ONE
author_facet Stefan Ryser
Edgar Tenorio
Angeles Estellés
Lawrence M Kauvar
author_sort Stefan Ryser
title 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_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_sort human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2019-01-01
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.
url https://doi.org/10.1371/journal.pone.0219256
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