Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection

David Skurnik, Michael R. Davis, Dennis Benedetti, Katie L. Moravec, Colette Cywes-Bentley, Damien Roux, David C. Traficante, Rebecca L. Walsh, Tomas Maira-Litrn, Sara K. Cassidy, Christina R. Hermos, Thomas R. Martin, Erin L. Thakkallapalli, Sara O. Vargas, Alexander J. McAdam, Tami D. Lieberman, Roy Kishony, John J. Lipuma, Gerald B. Pier, Joanna B. GoldbergGregory P. Priebe

Research output: Contribution to journalArticlepeer-review


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.MethodsThe 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.ResultsPNAG 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.

Original languageEnglish
Pages (from-to)1709-1718
Number of pages10
JournalJournal of Infectious Diseases
Issue number11
StatePublished - 1 Jun 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases


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