title: Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins.
abstract: Bacteria that cause chronic and/or recurrent diseases often rely on a biofilm lifestyle. The foundation of the biofilm structure is the extracellular polymeric substance (EPS) that acts as a barrier to both effectors of the immune system and antimicrobial agents. Recent work has highlighted extracellular DNA (eDNA) as a key component common to many pathogenic biofilms. Here, we show that the DNABII family of proteins, well known for their strong structural influences on intracellular DNA, was also critical for the integrity of the EPS matrix of biofilms that contain eDNA. In fact, antisera derived against a purified Escherichia coli DNABII family member rapidly disrupts the biofilm EPS formed by multiple human pathogens in vitro. In addition, when a member of this family of proteins was used as an immunogen in an animal model in which the bacteria had already formed a robust biofilm at the site of infection, the resultant targeted immune response strongly ameliorated this biofilm disease in vivo. Finally, this methodology to debulk the biofilm of EPS was shown to work synergistically with otherwise ineffective traditional anti-microbial approaches in vitro. We discuss the prospects for targeting DNABII family members as a potential universal strategy for treating biofilm diseases.
authors.affiliation: Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA. sgoodman@usc.edu
authors.forename: S D
authors.initials: SD
authors.lastname: Goodman
authors.forename: K P
authors.initials: KP
authors.lastname: Obergfell
authors.forename: J A
authors.initials: JA
authors.lastname: Jurcisek
authors.forename: L A
authors.initials: LA
authors.lastname: Novotny
authors.forename: J S
authors.initials: JS
authors.lastname: Downey
authors.forename: E A
authors.initials: EA
authors.lastname: Ayala
authors.forename: N
authors.initials: N
authors.lastname: Tjokro
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: S S
authors.initials: SS
authors.lastname: Justice
authors.forename: L O
authors.initials: LO
authors.lastname: Bakaletz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001428:Bacterial Vaccines; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002682:Chinchilla; D004195:Disease Models, Animal; D018450:Disease Progression; D053488:DnaB Helicases / Q000494:pharmacology; D004432:Ear, Middle / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D006192:Haemophilus Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D006193:Haemophilus influenzae / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D034982:Integration Host Factors / Q000276:immunology; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D034982:Integration Host Factors; C506730:dnaB protein, E coli; D053488:DnaB Helicases