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.

antibodies, PNAG, Biofilm, protective immunity, Burkholderia cepacia complex (BCC), opsonophagocytic assays

NCBI PubMed ID: 22448004
Publication DOI: 10.1093/infdis/jis254
Journal NLM ID: 0413675
Publisher: Oxford: Oxford University Press
Correspondence: dskurnikrics.bwh.harvard.edu
Institutions: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Methods: biological assays, genetic methods, immunochemical methods, microscopy, statistical analysis
 

• Compound ID: 1030
  

  -6)-b-D-GlcpNAc-(1-

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  Structure type: homopolymer
  Trivial name: poly-β-1,6-GlcNAc (PGA), biofilm, poly-b-(1-6)-N-acetyl-D-glucosamine (PNAG), poly-β-N-acetyl-glucosamine (PNAG), PNAG, poly-N-acetylglucosamine, PNAG
  Compound class: CPS, EPS, O-polysaccharide, glucan, polysaccharide
  Reference(s) to other database(s): GTC:G36952FI, GlycomeDB:11210
  
   
  
  Burkholderia cepacia, Burkholderia dolosa
  CSDB ID 27320 (all data & tools)