title: Synthetic β-sheet forming peptide amphiphiles for treatment of fungal keratitis.
abstract: Fungal keratitis is a leading cause of ocular morbidity. It is frequently misdiagnosed as bacterial keratitis, causing a delay in proper treatment. Furthermore, due to the lack of safe and effective anti-fungal agents for clinical use, treatment of fugal keratitis remains a challenge. In recent years, antimicrobial peptides (AMPs) have received considerable attention as potent and broad-spectrum antimicrobial agents with the potential to overcome antibiotics resistance. We previously reported the design of short synthetic β-sheet forming peptides (IKIK)2-NH2 and (IRIK)2-NH2 with excellent antimicrobial activities and selectivities against various clinically relevant microorganisms, including Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans (C. albicans). In this study, we evaluated the application of the two most promising synthetic β-sheet forming peptide candidates for in vivo fungal keratitis treatment in comparison with the commercially available amphotericin B. It was found that topical solutions of the designed peptides are safe, and as effective as the clinically used amphotericin B. Compared to the costly and unstable amphotericin B, (IKIK)2-NH2 and (IRIK)2-NH2 are water-soluble, less expensive and stable. Thus, the synthetic β-sheet forming peptides are presented as promising candidates for the treatment of fungal keratitis.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Zhan Yuin
authors.initials: ZY
authors.lastname: Ong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Nikken
authors.initials: N
authors.lastname: Wiradharma
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. Electronic address: yyyang@ibn.a-star.edu.sg.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. Electronic address: jyying@ibn.a-star.edu.sg.
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Ying
mesh_terms: D000666:Amphotericin B / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects; D018533:Biomass; D002176:Candida albicans / Q000187:drug effects; D002470:Cell Survival; D003261:Contact Lenses; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D000666:Amphotericin B
keywords: Anti-biofilm; Antibiotics resistance; Antifungal; Fungal keratitis; β-sheet forming peptide