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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. 205:1709-1718
- Publication Year :
- 2012
- Publisher :
- Oxford University Press (OUP), 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. 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.
- Subjects :
- Blood Bactericidal Activity
Klebsiella pneumoniae
Biology
medicine.disease_cause
Microbiology
Bacterial genetics
Mice
Major Articles and Brief Reports
Phagocytosis
medicine
Animals
Immunology and Allergy
integumentary system
Burkholderia cepacia complex
Polysaccharides, Bacterial
Biofilm
Burkholderia Infections
biology.organism_classification
Antibodies, Bacterial
Virology
Disease Models, Animal
Stenotrophomonas maltophilia
Infectious Diseases
Staphylococcus aureus
Female
Immunotherapy
Enterobacter cloacae
Bacteria
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 205
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....6ba30d531a4bf16cff9b1263affd39c0