Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis.
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.
Published In/Presented At
Chennupati, S. K., Chiu, A. G., Tamashiro, E., Banks, C. A., Cohen, M. B., Bleier, B. S., Kofonow, J. M., Tam, E., & Cohen, N. A. (2009). Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis. American journal of rhinology & allergy, 23(1), 46–51. https://doi.org/10.2500/ajra.2009.23.3261
Medicine and Health Sciences
Department of Pediatrics, Department of Surgery