Effects of an LL-37-derived antimicrobial peptide in an animal model of
biofilm Pseudomonas sinusitis.
Chennupati SK, Chiu AG, Tamashiro E, Banks CA, Cohen MB, Bleier BS,
Kofonow JM, Tam E, Cohen NA.
Department of Otorhinolaryngology-Head and Neck Surgery, University of
Pennsylvania, Philadelphia, Pennsylvania, USA.

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.

Publication Types:
*  Research Support, Non-U.S. Gov't

PMID: 19379612