Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis

Sri Kiran Chennupati, Alexander G Chiu, Edwin Tamashiro, Caroline A. Banks, Michael B. Cohen, Benjamin S. Bleier, Jennifer M. Konofow, Eric Tam, Noam A. Cohen

Research output: Contribution to journalArticle

61 Citations (Scopus)

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 400× 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.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalAmerican Journal of Rhinology and Allergy
Volume23
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Sinusitis
Biofilms
Pseudomonas
Animal Models
Peptides
Tobramycin
Mucous Membrane
Pseudomonas aeruginosa
Inflammation
Bacterial Load
Microbial Sensitivity Tests
Nose
Innate Immunity
antimicrobial peptide LL-37
Stem Cells
Catheters
Rabbits
Amino Acids
Bone and Bones
Infection

Keywords

  • Animal model
  • Antimicrobial peptide
  • Biofilm
  • Cathelicidin
  • LL-37
  • Pseudomonas
  • Sinusitis
  • Topical therapies

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Immunology and Allergy

Cite this

Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis. / Chennupati, Sri Kiran; Chiu, Alexander G; Tamashiro, Edwin; Banks, Caroline A.; Cohen, Michael B.; Bleier, Benjamin S.; Konofow, Jennifer M.; Tam, Eric; Cohen, Noam A.

In: American Journal of Rhinology and Allergy, Vol. 23, No. 1, 01.2009, p. 46-51.

Research output: Contribution to journalArticle

Chennupati, SK, Chiu, AG, Tamashiro, E, Banks, CA, Cohen, MB, Bleier, BS, Konofow, JM, Tam, E & Cohen, NA 2009, 'Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis', American Journal of Rhinology and Allergy, vol. 23, no. 1, pp. 46-51. https://doi.org/10.2500/ajra.2009.23.3261
Chennupati, Sri Kiran ; Chiu, Alexander G ; Tamashiro, Edwin ; Banks, Caroline A. ; Cohen, Michael B. ; Bleier, Benjamin S. ; Konofow, Jennifer M. ; Tam, Eric ; Cohen, Noam A. / Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis. In: American Journal of Rhinology and Allergy. 2009 ; Vol. 23, No. 1. pp. 46-51.
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AU - Cohen, Michael B.

AU - Bleier, Benjamin S.

AU - Konofow, Jennifer M.

AU - Tam, Eric

AU - Cohen, Noam A.

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AB - 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 400× 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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