| Summary: | <p>Abstract</p> <p>Background</p> <p><it>Pseudomonas aeruginosa</it> and <it>Burkholderia cepacia</it> infections of cystic fibrosis patients' lungs are often resistant to conventional antibiotic therapy. Protegrins are antimicrobial peptides with potent activity against many bacteria, including <it>P. aeruginosa</it>. The present study evaluates the correlation between protegrin-1 (PG-1) sensitivity/resistance and protegrin binding in <it>P. aeruginosa</it> and <it>B. cepacia</it>.</p> <p>Methods</p> <p>The PG-1 sensitivity/resistance and PG-1 binding properties of <it>P. aeruginosa</it> and <it>B. cepacia</it> were assessed using radial diffusion assays, radioiodinated PG-1, and surface plasmon resonance (BiaCore).</p> <p>Results</p> <p>The six <it>P. aeruginosa</it> strains examined were very sensitive to PG-1, exhibiting minimal active concentrations from 0.0625–0.5 μg/ml in radial diffusion assays. In contrast, all five <it>B. cepacia</it> strains examined were greater than 10-fold to 100-fold more resistant, with minimal active concentrations ranging from 6–10 μg/ml. When incubated with a radioiodinated variant of PG-1, a sensitive <it>P. aeru</it>ginosa strain bound considerably more protegrin molecules per cell than a resistant <it>B. cepacia</it> strain. Binding/diffusion and surface plasmon resonance assays revealed that isolated lipopolysaccharide (LPS) and lipid A from the sensitive <it>P. aeruginosa</it> strains bound PG-1 more effectively than LPS and lipid A from resistant <it>B. cepacia</it> strains.</p> <p>Conclusion</p> <p>These findings support the hypothesis that the relative resistance of <it>B. cepacia</it> to protegrin is due to a reduced number of PG-1 binding sites on the lipid A moiety of its LPS.</p>
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