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Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2012 Jun; Vol. 205 (11), pp. 1709-18. Date of Electronic Publication: 2012 Mar 23. - Publication Year :
- 2012
-
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.<br />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.<br />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.<br />Conclusions: Our findings raise potential new therapeutic options against PNAG-producing bacteria, including even pan-resistant pathogens.
- Subjects :
- Animals
Antibodies, Bacterial administration & dosage
Blood Bactericidal Activity
Burkholderia cepacia complex immunology
Disease Models, Animal
Female
Immunotherapy methods
Mice
Phagocytosis
Antibodies, Bacterial immunology
Burkholderia Infections therapy
Burkholderia cepacia complex drug effects
Polysaccharides, Bacterial immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 205
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 22448004
- Full Text :
- https://doi.org/10.1093/infdis/jis254