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. 2022 May 23;21(1):e124017.
doi: 10.5812/ijpr-124017. eCollection 2022 Dec.

In Silico Design and In Vitro Evaluation of Some Novel AMPs Derived From Human LL-37 as Potential Antimicrobial Agents for Keratitis

Arsalan Pashapour  1 , Soroush Sardari  1 , Parastoo Ehsani  2
Affiliations

In Silico Design and In Vitro Evaluation of Some Novel AMPs Derived From Human LL-37 as Potential Antimicrobial Agents for Keratitis

Arsalan Pashapour et al. Iran J Pharm Res. .

Abstract

The human body produces two classes of antimicrobial peptides (AMPs), namely defensins and cathelicidins. In this study, a novel decapeptide (Catoid) and its dimer (Dicatoid) based on human cathelicidin (LL-37) have been designed by bioinformatics tools to be used in the treatment of bacterial keratitis. After the selection and synthesis of peptide sequences, their antimicrobial activities against the standard and resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. This test was performed with LL-37, gentamicin, ciprofloxacin, amikacin, and penicillin for a more accurate comparison. Furthermore, the cytotoxicity levels of the specified compounds on fibroblast cells and bovine corneal endothelial cells were investigated. The results demonstrated that the designed peptides had a superior antimicrobial activity on P. aeruginosa, compared to LL-37; however, Catoid had a better effect on the S. aureus strain. Additionally, a significant achievement is the very low toxicity level of Catoid and Dicatoid on the human skin fibroblast cell line and bovine corneal endothelial cells, compared to that of LL-37 as the initial design model.

Keywords: Antimicrobial Peptides (AMPs); Bacterial Keratitis; Bovine Corneal Endothelial Cells; Cathelicidin; Catoid; Dicatoid.

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Conflict of interest statement

Conflict of Interests: The authors have no conflict of interest to declare.

Figures

Figure 1.
Figure 1.. Catoid structure
Figure 2.
Figure 2.. Dicatoid structure
Figure 3.
Figure 3.. Isolated bovine cornea
Figure 4.
Figure 4.. Antimicrobial peptide probability score of sequences in three different algorithms: support vector machine (SVM), random forest (RF), and discriminant analysis (DA)
Figure 5.
Figure 5.. Total sum-up for antimicrobial peptide probability of sequences
Figure 6.
Figure 6.. Comparison of antimicrobial peptide probability scores in designed peptides and ll-37 in three different algorithms: support vector machine (SVM), random forest (RF), and discriminant analysis (DA)
Figure 7.
Figure 7.. In silico toxicity prediction of Catoid and Dicatoid
Figure 8.
Figure 8.. MTT assay on human fibroblast cells
Figure 9.
Figure 9.. Half-maximal inhibitory concentration (IC50) values of designed peptides
Figure 10.
Figure 10.. Dual Staining of Corneal Endothelial Cells Treated with Different Antimicrobial Agents; A) Doxorubicin, B) Dicatoid, C) Ciprofloxacin, D) Catoid, and E) LL-37
See this image and copyright information in PMC

References

    1. Clemens LE, Jaynes J, Lim E, Kolar SS, Reins RY, Baidouri H, et al. Designed Host Defense Peptides for the Treatment of Bacterial Keratitis. Invest Ophthalmol Vis Sci. 2017;58(14):6273–81. doi: 10.1167/iovs.17-22243. - DOI - PMC - PubMed
    1. Ting DSJ, Ho CS, Deshmukh R, Said DG, Dua HS. Correction to: Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye (Lond). 2021;35(10):2908. doi: 10.1038/s41433-021-01568-0. - DOI - PMC - PubMed
    1. Ting DSJ, Ho CS, Cairns J, Elsahn A, Al-Aqaba M, Boswell T, et al. 12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study. Br J Ophthalmol. 2021;105(3):328–33. doi: 10.1136/bjophthalmol-2020-316128. - DOI - PMC - PubMed
    1. Stapleton F, Carnt N. Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis. Eye (Lond). 2012;26(2):185–93. doi: 10.1038/eye.2011.288. - DOI - PMC - PubMed
    1. Urwin L, Okurowska K, Crowther G, Roy S, Garg P, Karunakaran E, et al. Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis. Cells. 2020;9(11) doi: 10.3390/cells9112450. - DOI - PMC - PubMed

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