title: A bacterial-biofilm-induced oral osteolytic infection can be successfully treated by immuno-targeting an extracellular nucleoid-associated protein.
abstract: Periodontal disease exemplifies a chronic and recurrent infection with a necessary biofilm component. Mucosal inflammation is a hallmark response of the host seen in chronic diseases, such as colitis, gingivitis, and periodontitis (and the related disorder peri-implantitis). We have taken advantage of our recently developed rat model of human peri-implantitis that recapitulates osteolysis, the requirement of biofilm formation, and the perpetuation of the bona fide disease state, to test a new therapeutic modality with two novel components. First we used hyperimmune antiserum directed against the DNABII family of proteins, now known to be a critical component of the extracellular matrix of bacterial biofilms. Second we delivered the antiserum as cargo in biodegradable microspheres to the site of the biofilm infection. We demonstrated that delivery of a single dose of anti-DNABII in poly(lactic-co-glycolic acid) (PLGA) microspheres induced significant resolution of experimental peri-implantitis, including marked reduction of inflammation. These data support the continued development of a DNABII protein-targeted therapeutic for peri-implantitis and other chronic inflammatory pathologies of the oral cavity in animals and humans.
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, USA.|Department of Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: M O
authors.identifier: 0000-0003-4906-7698
authors.initials: MO
authors.lastname: Freire
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Devaraj
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Young
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Navarro
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Downey
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: L O
authors.initials: LO
authors.lastname: Bakaletz
authors.affiliation: Division of Periodontology, Diagnostic Sciences & Dental Hygiene Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.|Laboratory for Immunoregulation and Tissue Engineering (LITE), University of Southern California, Los Angeles, CA, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Zadeh
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D015921:Dental Implants / Q000382:microbiology; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D034982:Integration Host Factors / Q000276:immunology; D019344:Lactic Acid / Q000494:pharmacology; D008863:Microspheres; D010014:Osteolysis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D057873:Peri-Implantitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D010518:Periodontitis / Q000382:microbiology*; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004268:DNA-Binding Proteins; D015921:Dental Implants; D029968:Escherichia coli Proteins; D034982:Integration Host Factors; C440502:integration host factor, E coli; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: 
  Aggregatibacter actinomycetemcomitans
  ; DNABII protein; biofilm; inflammation; integration host factor