Esculentin-1a derived peptides kill Pseudomonas aeruginosa biofilm on soft contact lenses and retain antibacterial activity upon immobilization to the lens surface

Bruno Casciaro, Debarun Dutta, Maria Rosa Loffredo, Stefania Marcheggiani, Alison M McDermott, Mark Dp Willcox, Maria Luisa Mangoni

Research output: Contribution to journalArticle

Abstract

Contact lens (CL) wear is a risk factor for development of microbial keratitis, a vision threatening infection of the eye. Adverse events associated with colonization of lenses, especially by the multi-drug resistant and biofilm forming bacterium Pseudomonas aeruginosa remain a major safety issue. Therefore, novel strategies and compounds to reduce the onset of CL-associated ocular infections are needed. Recently, the activity of the frog skin-derived antimicrobial peptide Esc(1-21) and its diastereomer Esc(1-21)-1c was evaluated against both planktonic and sessile forms of this pathogen. Furthermore, Esc(1-21) was found to significantly reduce the severity of P. aeruginosa keratitis in a mouse model and preserve antipseudomonal activity in the presence of human basal tears. Here, we have analyzed the activity of the peptides on P. aeruginosa biofilm formed on soft CLs. Microbiological assays and scanning electron microscopy analysis indicated that the peptides were able to disrupt the bacterial biofilm, with the diastereomer having the greater efficacy (up to 85% killing vs no killing at 4 μM for some strains). Furthermore, upon covalent immobilization to the CL, the two peptides were found to cause more than four log reduction in the number of bacterial cells within 20 minutes and to reduce bacterial adhesion to the CL surface (77%-97% reduction) in 24 hours. Importantly, peptide immobilization was not toxic to mammalian cells and did not affect the lens characteristics. Overall, our data suggest that both peptides have great potential to be developed as novel pharmaceuticals for prevention and treatment of CL-associated P. aeruginosa keratitis.

Original languageEnglish
Article numbere23074
JournalBiopolymers
Volume110
Issue number5
Early online date16 Feb 2018
DOIs
Publication statusPublished - 1 Sep 2018

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Contact lenses
Hydrophilic Contact Lens
Contact Lenses
Biofilms
Immobilization
Pseudomonas aeruginosa
Peptides
Lenses
Keratitis
Eye Infections
Bacterial Adhesion
Poisons
Tears
Pharmaceutical Preparations
Anura
Electron Scanning Microscopy
Pathogens
Drug products
Cell Count
esculentin steroid

Bibliographical note

© 2017 Wiley Periodicals, Inc.

Cite this

Casciaro, B., Dutta, D., Loffredo, M. R., Marcheggiani, S., McDermott, A. M., Willcox, M. D., & Mangoni, M. L. (2018). Esculentin-1a derived peptides kill Pseudomonas aeruginosa biofilm on soft contact lenses and retain antibacterial activity upon immobilization to the lens surface. Biopolymers, 110(5), [e23074]. https://doi.org/10.1002/bip.23074
Casciaro, Bruno ; Dutta, Debarun ; Loffredo, Maria Rosa ; Marcheggiani, Stefania ; McDermott, Alison M ; Willcox, Mark Dp ; Mangoni, Maria Luisa. / Esculentin-1a derived peptides kill Pseudomonas aeruginosa biofilm on soft contact lenses and retain antibacterial activity upon immobilization to the lens surface. In: Biopolymers. 2018 ; Vol. 110, No. 5.
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abstract = "Contact lens (CL) wear is a risk factor for development of microbial keratitis, a vision threatening infection of the eye. Adverse events associated with colonization of lenses, especially by the multi-drug resistant and biofilm forming bacterium Pseudomonas aeruginosa remain a major safety issue. Therefore, novel strategies and compounds to reduce the onset of CL-associated ocular infections are needed. Recently, the activity of the frog skin-derived antimicrobial peptide Esc(1-21) and its diastereomer Esc(1-21)-1c was evaluated against both planktonic and sessile forms of this pathogen. Furthermore, Esc(1-21) was found to significantly reduce the severity of P. aeruginosa keratitis in a mouse model and preserve antipseudomonal activity in the presence of human basal tears. Here, we have analyzed the activity of the peptides on P. aeruginosa biofilm formed on soft CLs. Microbiological assays and scanning electron microscopy analysis indicated that the peptides were able to disrupt the bacterial biofilm, with the diastereomer having the greater efficacy (up to 85{\%} killing vs no killing at 4 μM for some strains). Furthermore, upon covalent immobilization to the CL, the two peptides were found to cause more than four log reduction in the number of bacterial cells within 20 minutes and to reduce bacterial adhesion to the CL surface (77{\%}-97{\%} reduction) in 24 hours. Importantly, peptide immobilization was not toxic to mammalian cells and did not affect the lens characteristics. Overall, our data suggest that both peptides have great potential to be developed as novel pharmaceuticals for prevention and treatment of CL-associated P. aeruginosa keratitis.",
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Esculentin-1a derived peptides kill Pseudomonas aeruginosa biofilm on soft contact lenses and retain antibacterial activity upon immobilization to the lens surface. / Casciaro, Bruno; Dutta, Debarun; Loffredo, Maria Rosa; Marcheggiani, Stefania; McDermott, Alison M; Willcox, Mark Dp; Mangoni, Maria Luisa.

In: Biopolymers, Vol. 110, No. 5, e23074, 01.09.2018.

Research output: Contribution to journalArticle

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AU - Casciaro, Bruno

AU - Dutta, Debarun

AU - Loffredo, Maria Rosa

AU - Marcheggiani, Stefania

AU - McDermott, Alison M

AU - Willcox, Mark Dp

AU - Mangoni, Maria Luisa

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