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Int J Mol Sci. 2019 Jan 17;20(2). pii: E393. doi: 10.3390/ijms20020393.

Antibacterial Activities of Lipopeptide (C10)₂-KKKK-NH₂ Applied Alone and in Combination with Lens Liquids to Fight Biofilms Formed on Polystyrene Surfaces and Contact Lenses.

Author information

1
Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. mdawgul@gumed.edu.pl.
2
Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. maciejewska.kj@gmail.com.
3
Pharmaceutical Laboratory Avena Sp.z.o.o., 86-031 Osielsko, Poland. maciejewska.kj@gmail.com.
4
Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. greber@gumed.edu.pl.
5
Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. wsawicki@gumed.edu.pl.
6
Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. kamysz@gumed.edu.pl.

Abstract

The widespread use of biomaterials such as contact lenses is associated with the development of biofilm-related infections which are very difficult to manage with standard therapies. The formation of bacterial biofilms on the surface of biomaterials is associated with increased antibiotic resistance. Owing to their promising antimicrobial potential, lipopeptides are being intensively investigated as novel antimicrobials. However, due to the relatively high toxicity exhibited by numerous compounds, a lot of attention is being paid to designing new lipopeptides with optimal biological activities. The principal aim of this study was to evaluate the potential ophthalmic application of lipopeptide (C10)₂-KKKK-NH₂. This lipopeptide was synthesized according to Fmoc chemistry using the solid-phase method. The antibiofilm activities of the lipopeptide, antibiotics used in ocular infections, and commercially available lens liquids were determined using the broth dilution method on polystyrene 96-well plates and contact lenses. Resazurin was applied as the cell-viability reagent. The effectiveness of the commercially available lens liquids supplemented with the lipopeptide was evaluated using the same method and materials. (C10)₂-KKKK-NH₂ exhibited stronger anti-biofilm properties compared to those of the tested conventional antimicrobials and showed the ability to enhance the activity of lens liquids at relatively low concentrations (4⁻32 mg/L). Estimation of the eye irritation potential of the lipopeptide using Toxtree software 2.6.13 suggests that the compound could be safely applied on the human eye. The results of performed experiments encourage further studies on (C10)₂-KKKK-NH₂ and its potential application in the prophylaxis of contact lens-related eye infections.

KEYWORDS:

biofilm; biofilm on contact lenses; lipopeptides; ocular infections; persister cells

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