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

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.

Self-disinfecting surfaces and infection control

“…Antimicrobial peptides (AMPs) are a class of peptides, components of innate immune system, with a broad activity against bacteria, virus, fungus and more, providing a non-specific defense against a broad spectrum of invaders [110]. Recently, numerous studies [111,112] refer its use as antimicrobial loading agents for their excellent characteristics, presenting several advantages over classic antibiotics, namely fast and broad spectrum of action with low susceptibility to induce bacterial resistance [113]. In contrast with the mechanisms of action of antibiotics, which are based in slow processes of enzymatic inhibition and target specific cellular activities as DNA or protein, the AMPs are effective against different species of microorganisms and also reduce the risk of resistance development [113][114][115].…”

“…In a recent study, Casciaro et al [111] successfully covalently immobilized frog skin derived AMP on contact lenses. This strategy not only reduced the adhesion of P. aeruginosa, a species highly associated with contact lenses associated keratitis, but it also proved to be nontoxic to mammalian cells and it did not compromise the lenses physical properties.…”

Biofilm modelling on the contact lenses and comparison of the in vitro activities of multipurpose lens solutions and antibiotics

“…AMP coated CL is the most promising one among them, due to the AMPs excellent antibiofilm activities against mature or immature biofilms (Dosler & Karaaslan, 2014). Casciaro et al (2018) have demonstrated that the frog skin AMP Esculentin-1a derived peptides represented encouraging candidates to be developed as ophthalmic formulations and/or for the manufacturing an antimicrobial CLs in order to prevent them from infections.…”

Antimicrobial peptides – Advances in development of therapeutic applications

“… AMPs Surface/Devices Antimicrobial activity Ref. Esc(1–21) Contact lens Disrupt the bacterial biofilm Reduce the number of bacterial cells within 20 min and bacterial adhesion to the CL surface (77%–97% reduction) in 24 h [ 237 ] RRWRIVVIRVRRC Catheter The antimicrobial peptide coating prevented both Gram-positive and Gram-negative bacterial adhesion by up to 99.9% and inhibited planktonic bacterial growth by up to 70%. In vivo , the peptide coating was tested in a mouse urinary catheter infection model.…”