title: Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.
abstract: BACKGROUND
  New therapeutic targets for antibiotic-resistant bacterial pathogens are desperately needed. The bacterial surface polysaccharide poly-β-(1-6)-N-acetyl-glucosamine (PNAG) mediates biofilm formation by some bacterial species, and antibodies to PNAG can confer protective immunity. By analyzing sequenced genomes, we found that potentially multidrug-resistant bacterial species such as Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia, and the Burkholderia cepacia complex (BCC) may be able to produce PNAG. Among patients with cystic fibrosis patients, highly antibiotic-resistant bacteria in the BCC have emerged as problematic pathogens, providing an impetus to study the potential of PNAG to be targeted for immunotherapy against pan-resistant bacterial pathogens.
  
  
  METHODS
  The presence of PNAG on BCC was assessed using a combination of bacterial genetics, microscopy, and immunochemical approaches. Antibodies to PNAG were tested using opsonophagocytic assays and for protective efficacy against lethal peritonitis in mice.
  
  
  RESULTS
  PNAG is expressed in vitro and in vivo by the BCC, and cystic fibrosis patients infected by the BCC species B. dolosa mounted a PNAG-specific opsonophagocytic antibody response. Antisera to PNAG mediated opsonophagocytic killing of BCC and were protective against lethal BCC peritonitis even during coinfection with methicillin-resistant Staphylococcus aureus.
  
  
  CONCLUSIONS
  Our findings raise potential new therapeutic options against PNAG-producing bacteria, including even pan-resistant pathogens.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. dskurnik@rics.bwh.harvard.edu
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.forename: Michael R
authors.initials: MR
authors.lastname: Davis
authors.forename: Dennis
authors.initials: D
authors.lastname: Benedetti
authors.forename: Katie L
authors.initials: KL
authors.lastname: Moravec
authors.forename: Colette
authors.initials: C
authors.lastname: Cywes-Bentley
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.forename: David C
authors.initials: DC
authors.lastname: Traficante
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Walsh
authors.forename: Tomas
authors.initials: T
authors.lastname: Maira-Litràn
authors.forename: Sara K
authors.initials: SK
authors.lastname: Cassidy
authors.forename: Christina R
authors.initials: CR
authors.lastname: Hermos
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: Erin L
authors.initials: EL
authors.lastname: Thakkallapalli
authors.forename: Sara O
authors.initials: SO
authors.lastname: Vargas
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: McAdam
authors.forename: Tami D
authors.initials: TD
authors.lastname: Lieberman
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
authors.forename: John J
authors.initials: JJ
authors.lastname: Lipuma
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001770:Blood Bactericidal Activity; D019121:Burkholderia Infections / Q000628:therapy*; D042602:Burkholderia cepacia complex / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D011135:Polysaccharides, Bacterial