title: Binding of protegrin-1 to Pseudomonas aeruginosa and Burkholderia cepacia.
abstract: BACKGROUND
  Pseudomonas aeruginosa and Burkholderia cepacia infections of cystic fibrosis patients' lungs are often resistant to conventional antibiotic therapy. Protegrins are antimicrobial peptides with potent activity against many bacteria, including P. aeruginosa. The present study evaluates the correlation between protegrin-1 (PG-1) sensitivity/resistance and protegrin binding in P. aeruginosa and B. cepacia.
  
  
  METHODS
  The PG-1 sensitivity/resistance and PG-1 binding properties of P. aeruginosa and B. cepacia were assessed using radial diffusion assays, radioiodinated PG-1, and surface plasmon resonance (BiaCore).
  
  
  RESULTS
  The six P. aeruginosa strains examined were very sensitive to PG-1, exhibiting minimal active concentrations from 0.0625-0.5 microg/ml in radial diffusion assays. In contrast, all five B. cepacia strains examined were greater than 10-fold to 100-fold more resistant, with minimal active concentrations ranging from 6-10 microg/ml. When incubated with a radioiodinated variant of PG-1, a sensitive P. aeruginosa strain bound considerably more protegrin molecules per cell than a resistant B. cepacia strain. Binding/diffusion and surface plasmon resonance assays revealed that isolated lipopolysaccharide (LPS) and lipid A from the sensitive P. aeruginosa strains bound PG-1 more effectively than LPS and lipid A from resistant B. cepacia strains.
  
  
  CONCLUSIONS
  These findings support the hypothesis that the relative resistance of B. cepacia to protegrin is due to a reduced number of PG-1 binding sites on the lipid A moiety of its LPS.
authors: Division of Biomedical Sciences, University of California, Riverside, California 92521, USA. mark.albrecht@ucr.edu <mark.albrecht@ucr.edu>
authors: Mark T
authors: MT
authors: Albrecht
authors: Wei
authors: W
authors: Wang
authors: Olga
authors: O
authors: Shamova
authors: Robert I
authors: RI
authors: Lehrer
authors: Neal L
authors: NL
authors: Schiller
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D016956:Burkholderia cepacia / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D006801:Humans; D008050:Lipid A / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008050:Lipid A; D008070:Lipopolysaccharides; D011506:Proteins; C094880:protegrin-1