Contact lens wear is an important risk factor for microbial keratitis, a potentially vision threatening infection of the eye (1). Adverse events associated with microbial adhesion and colonization of lenses, especially by the biofilm forming Gram-negative bacterium Pseudomonas aeruginosa remain a major safety issue. This is further complicated by the increase in bacterial resistance to traditional antibiotics. Therefore, novel strategies to prevent and treat contact lens-associated keratitis are greatly needed. An important approach is the development of agents that hamper pathogen attachment and biofilm formation in the first place. Naturally occurring antimicrobial peptides (AMPs) hold particular promise in this regard. Esculentins are a family of AMPs derived from amphibian skin with a wide spectrum of antimicrobial activity. Esculentin-1a(1-21)NH2 [Esc(1-21)], that consists of the first 20 amino acids of the native Esculentin-1a, with a glycinamide residue at the C-terminus, is a novel AMP with a potent activity against both free-living and sessile forms of P. aeruginosa (2). Previous studies have shown its anti-Pseudomonal activity in the presence of human basal tears as well as a reduction of infection in a mouse model of P. aeruginosa keratitis (3). Here we investigated the peptide’s ability to inhibit and/or to disrupt biofilm formation on soft contact lenses using both reference strains and clinical isolates of P. aeruginosa. The percentage of surviving cells was evaluated by the 3(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide (MTT) assay. Our results indicate that Esc(1-21) is able to eradicate biofilm cells from contact-lenses at a concentration range of 4-16 μM, and to inhibit Pseudomonas biofilm when used at lower concentrations. The effects of Esc(1-21) on the morphology of biofilm cells on contact lenses were also visualized by scanning electron microscopy. Overall, our data suggest that Esc(1-21) has great potential for development as a novel pharmaceutical for prevention and treatment of contact lens-associated P. aeruginosa keratitis. (1) (1) Robertson DM. Eye Contact Lens. 2013 Jan;39(1):67-72 (2) (2) Luca V et al. Cell Mol Life Sci. 2013 Aug;70(15):2773-86 (3) (3) Kolar SS et al. Cell Mol Life Sci. 2015 Feb;72(3):617-27

Esculentin-1a(1-21)NH2: a promising peptide for prevention and eradicatin of Pseudomonas aeruginosa biofilm formation on soft contact-lenses

CASCIARO, BRUNO;LUCA, VINCENZO;CAPPIELLO, FLORIANA;MANGONI, Maria Luisa
2015

Abstract

Contact lens wear is an important risk factor for microbial keratitis, a potentially vision threatening infection of the eye (1). Adverse events associated with microbial adhesion and colonization of lenses, especially by the biofilm forming Gram-negative bacterium Pseudomonas aeruginosa remain a major safety issue. This is further complicated by the increase in bacterial resistance to traditional antibiotics. Therefore, novel strategies to prevent and treat contact lens-associated keratitis are greatly needed. An important approach is the development of agents that hamper pathogen attachment and biofilm formation in the first place. Naturally occurring antimicrobial peptides (AMPs) hold particular promise in this regard. Esculentins are a family of AMPs derived from amphibian skin with a wide spectrum of antimicrobial activity. Esculentin-1a(1-21)NH2 [Esc(1-21)], that consists of the first 20 amino acids of the native Esculentin-1a, with a glycinamide residue at the C-terminus, is a novel AMP with a potent activity against both free-living and sessile forms of P. aeruginosa (2). Previous studies have shown its anti-Pseudomonal activity in the presence of human basal tears as well as a reduction of infection in a mouse model of P. aeruginosa keratitis (3). Here we investigated the peptide’s ability to inhibit and/or to disrupt biofilm formation on soft contact lenses using both reference strains and clinical isolates of P. aeruginosa. The percentage of surviving cells was evaluated by the 3(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide (MTT) assay. Our results indicate that Esc(1-21) is able to eradicate biofilm cells from contact-lenses at a concentration range of 4-16 μM, and to inhibit Pseudomonas biofilm when used at lower concentrations. The effects of Esc(1-21) on the morphology of biofilm cells on contact lenses were also visualized by scanning electron microscopy. Overall, our data suggest that Esc(1-21) has great potential for development as a novel pharmaceutical for prevention and treatment of contact lens-associated P. aeruginosa keratitis. (1) (1) Robertson DM. Eye Contact Lens. 2013 Jan;39(1):67-72 (2) (2) Luca V et al. Cell Mol Life Sci. 2013 Aug;70(15):2773-86 (3) (3) Kolar SS et al. Cell Mol Life Sci. 2015 Feb;72(3):617-27
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/954650
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