title: Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo.
abstract: The vast majority of chronic and recurrent bacterial diseases are attributed to the presence of a recalcitrant biofilm that contributes significantly to pathogenesis. As such, these diseases will require an innovative therapeutic approach. We targeted DNABII proteins, an integral component of extracellular DNA (eDNA) which is universally found as part of the pathogenic biofilm matrix to develop a biofilm disrupting therapeutic. We show that a cocktail of monoclonal antibodies directed against specific epitopes of a DNABII protein is highly effective to disrupt diverse biofilms in vitro as well as resolve experimental infection in vivo, in both a chinchilla and murine model. Combining this monoclonal antibody cocktail with a traditional antibiotic to kill bacteria newly released from the biofilm due to the action of the antibody cocktail was highly effective. Our results strongly support these monoclonal antibodies as attractive candidates for lead optimization as a therapeutic for resolution of bacterial biofilm diseases.
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Department of Pediatrics, 700 Children's Drive, Columbus, OH, 43205, USA. Electronic address: Laura.Novotny@nationwidechildrens.org.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Novotny
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Department of Pediatrics, 700 Children's Drive, Columbus, OH, 43205, USA. Electronic address: Joseph.Jurcisek@nationwidechildrens.org.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jurcisek
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Department of Pediatrics, 700 Children's Drive, Columbus, OH, 43205, USA. Electronic address: Steven.Goodman@nationwidechildrens.org.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA; The Ohio State University College of Medicine, Department of Pediatrics, 700 Children's Drive, Columbus, OH, 43205, USA. Electronic address: Lauren.Bakaletz@nationwidechildrens.org.
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D000918:Antibody Specificity / Q000276:immunology; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D002682:Chinchilla; D004195:Disease Models, Animal; D053488:DnaB Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010033:Otitis Media / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D015203:Reproducibility of Results
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D010455:Peptides; D053488:DnaB Helicases
keywords: Histone like protein (HU); Integration host factor (IHF); Nontypeable Haemophilus influenzae; Otitis media; Pseudomonas aeruginosa; Respiratory tract infection