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

PLoS One. 2019 Jul 9;14(7):e0219256. doi: 10.1371/journal.pone.0219256. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Antibodies / analysis
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects*
  • Epitopes
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Single-Cell Analysis / methods

Substances

  • Anti-Bacterial Agents
  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bacterial Proteins
  • Epitopes
  • TRL1068

Grant support

All authors are employees or consultants with an equity interest in Trellis Bioscience LLC, which funded the study. The funder thereby had a role in study design, data collection and analysis, decision to publish, and preparation of the manuscript. Further, the funder has an issued US Patent (#10,233,234) on TRL1068 that is discussed in the manuscript, for which an IND is projected in the first half of 2020. Partial support was provided from an SBIR grant from US National Institute of Allergy and Infectious Diseases to LK: 5SB1AI120425-04, https://sbir.nih.gov/niaid/index.