AI Article Synopsis

  • LL-37 is a protein with antimicrobial properties that could help combat Pseudomonas aeruginosa biofilms in sinusitis.
  • Five groups of rabbits were infected with Pseudomonas and treated with varying concentrations of LL-37-derived peptides or a control, with results measured through infection levels and tissue analysis.
  • High concentrations of the peptide successfully reduced bacterial counts and eradicated biofilms, but also caused inflammation and damage to the cilia in the sinus mucosa.

Article Abstract

Background: LL-37, an innate immunity protein expressed within sinonasal mucosa, has in vitro antibacterial and antifungal properties as well as efficacy against preformed Pseudomonas aeruginosa biofilms. We hypothesize that a 24 amino acid peptide derivative of LL-37 will show efficacy against biofilm-forming P. aeruginosa in an established animal model of sinusitis.

Methods: Five groups of six New Zealand rabbits were each infected with P. aeruginosa (PAO-1) and fitted with irrigating catheters 7 days later. Each group was instilled with either one of three different concentrations of peptide, a positive control of topical tobramycin, or the carrier solution without the peptide once a day for 10 days. Nasal diluent was collected throughout the irrigation period to assess for persistence or resolution of infection by determining colony-forming units (CFU). At study end, sinus mucosa was harvested for histological assessment of inflammation and SEM evaluation for ciliary integrity and presence of biofilms.

Results: Topical tobramycin at 400x minimum inhibitory concentration and 2.5 mg/mL of peptide were effective in significantly lowering CFUs after 10 days of irrigation. Histological evaluation showed increased signs of inflammation in a dose-dependent manner within mucosa and bone of the groups receiving the peptide. SEM analysis showed ciliary loss in a dose-dependent manner. Biofilms were present in all groups except for the highest concentration of peptide and tobramycin.

Conclusion: High concentrations of LL-37-derived peptide showed in vivo ability to eradicate Pseudomonas biofilms and decrease bacterial counts. However, increasing concentrations of peptide showed proinflammatory and ciliotoxic effects on sinus mucosa.

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http://dx.doi.org/10.2500/ajra.2009.23.3261DOI Listing

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