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

Mohid, SA; Sharma, P; Alghalayini, A; Saini, T; Datta, D; Willcox, MDP; Ali, H; Raha, S; Singha, A; Lee, D; Sahoo, N; Cranfield, CG; Roy, S; Bhunia, A

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

Mohid, SA Sharma, P Alghalayini, A

Saini, T Datta, D Willcox, MDP Ali, H Raha, S Singha, A Lee, D Sahoo, N Cranfield, CG Roy, S Bhunia, A

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Biophysical Chemistry, 2022, 286, pp. 1-14
Issue Date:: 2022-07

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Field	Value	Language
dc.contributor.author	Mohid, SA
dc.contributor.author	Sharma, P
dc.contributor.author	Alghalayini, A https://orcid.org/0000-0002-2308-0256
dc.contributor.author	Saini, T
dc.contributor.author	Datta, D
dc.contributor.author	Willcox, MDP
dc.contributor.author	Ali, H
dc.contributor.author	Raha, S
dc.contributor.author	Singha, A
dc.contributor.author	Lee, D
dc.contributor.author	Sahoo, N
dc.contributor.author	Cranfield, CG
dc.contributor.author	Roy, S
dc.contributor.author	Bhunia, A
dc.date.accessioned	2022-12-13T02:20:03Z
dc.date.available	2022-03-15
dc.date.available	2022-12-13T02:20:03Z
dc.date.issued	2022-07
dc.identifier.citation	Biophysical Chemistry, 2022, 286, pp. 1-14
dc.identifier.issn	0301-4622
dc.identifier.issn	1873-4200
dc.identifier.uri	http://hdl.handle.net/10453/164341
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Biophysical Chemistry
dc.relation.isbasedon	10.1016/j.bpc.2022.106802
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	02 Physical Sciences, 03 Chemical Sciences, 06 Biological Sciences
dc.subject.classification	Biophysics
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Anti-Infective Agents
dc.subject.mesh	Antimicrobial Peptides
dc.subject.mesh	Eye Infections, Bacterial
dc.subject.mesh	Humans
dc.subject.mesh	Keratitis
dc.subject.mesh	Pseudomonas
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Anti-Infective Agents
dc.subject.mesh	Antimicrobial Peptides
dc.subject.mesh	Eye Infections, Bacterial
dc.subject.mesh	Humans
dc.subject.mesh	Keratitis
dc.subject.mesh	Pseudomonas
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Humans
dc.subject.mesh	Pseudomonas
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Eye Infections, Bacterial
dc.subject.mesh	Keratitis
dc.subject.mesh	Anti-Infective Agents
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Antimicrobial Peptides
dc.title	A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation.
dc.type	Journal Article
utslib.citation.volume	286
utslib.location.activity	Netherlands
utslib.for	02 Physical Sciences
utslib.for	03 Chemical Sciences
utslib.for	06 Biological Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-13T02:20:01Z
pubs.publication-status	Published
pubs.volume	286

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.

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http://hdl.handle.net/10453/164341