A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation

Abstract

Contact lens wearers are at an increased risk of developing Pseudomonas-associated corneal keratitis, which can lead to a host of serious ocular complications. Despite the use of topical antibiotics, ocular infections remain a major clinical problem, and a strategy to avoid Pseudomonas-associated microbial keratitis is urgently required. The hybrid peptide VR18 (VARGWGRKCPLFGKNKSR) was designed to have enhanced antimicrobial properties in the fight against Pseudomonas-induced microbial keratitis, including contact lens-related keratitis. In this paper, VR18's modes of action against Pseudomonas membranes were shown by live cell Raman spectroscopy, live cell NMR, live-cell fluorescence microscopy and measures taken using sparsely tethered bilayer lipid membrane bacterial models to be via a bacterial-specific membrane disruption mechanism. The high affinity and selectivity of the peptide were then demonstrated using in vivo, in vitro and ex vivo models of Pseudomonas infection. The extensive data presented in this work suggests that topical employment of the VR18 peptide would be a potent therapeutic agent for the prevention or remedy of Pseudomonas-associated microbial keratitis.

Publication DOI: https://doi.org/10.1016/j.bpc.2022.106802
Divisions: College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
Additional Information: © 2022 Elsevier B.V. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License https://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: Antimicrobial peptide (AMP),Bacterial keratitis,Contact lens,Nuclear magnetic resonance (NMR),Pseudomonas aeruginosa,Biophysics,Biochemistry,Organic Chemistry
Publication ISSN: 1873-4200
Last Modified: 08 Jul 2024 08:14
Date Deposited: 06 Jun 2022 13:41
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Related URLs: https://www.sci ... 0448?via%3Dihub (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-07-01
Published Online Date: 2022-03-22
Accepted Date: 2022-03-15
Submitted Date: 2022-01-28
Authors: Mohid, Sk Abdul
Sharma, Prerana
Alghalayini, Amani
Saini, Tripti
Datta, Debarun (ORCID Profile 0000-0002-2204-5272)
Willcox, Mark D P
Ali, Haydar
Raha, Sreyan
Singha, Achintya
Lee, DongKuk
Sahoo, Nirakar
Cranfield, Charles G
Roy, Sanhita
Bhunia, Anirban

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