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

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

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1
Trellis Bioscience LLC, Redwood City, California, United States of America.

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.

Conflict of interest statement

All authors are employees or consultants with an equity interest in Trellis Bioscience LLC, which funded the study and has filed patents on the technology, notably including issued US Patent No. 10,233,234. This patent includes claims to composition of matter of TRL1068 which is in preclinical development with an IND 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. Consistent with NIH funding policy, we confirm that the proprietary aspects of the project do not alter our adherence to PLOS ONE policies on sharing data and materials.

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