Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing

Floriana Cappiello, Sudhir Verma, Xiao Lin, Isabel Y. Moreno, Bruno Casciaro, Debarun Dutta, Alison M. McDermott, Mark Willcox, Vivien J. Coulson-Thomas, Maria Luisa Mangoni

Research output: Contribution to journalArticlepeer-review

Abstract

The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range.
Original languageEnglish
Article number1028
Number of pages14
JournalBiomolecules
Volume13
Issue number7
Early online date23 Jun 2023
DOIs
Publication statusPublished - Jul 2023

Bibliographical note

Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Funding: This research was supported by EU funding within the NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT, node 3) to M.L.M.; Pasteur-Italia Fondazione Cenci Bolognetti-Anna Tramontano grant 2018 to M.L.M.; the National Institute of Health/National Eye Institute R01 EY029289 and R01 EY033024 to V.J.C.-T. and core grant P30 EY07551; and funds from the Lions Foundation for Sight.

Keywords

  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Corneal Injuries/drug therapy
  • Keratitis/drug therapy
  • Mice
  • Peptides/therapeutic use
  • Pseudomonas Infections/drug therapy
  • Pseudomonas aeruginosa
  • Wound Healing

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