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The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii

Acanthamoeba is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of Acanthamoeba keratitis is challenging as Acanthamoeba can encyst from the active form, a trophozoite, into a hibernating cyst that is refractory to antibiotics and diff...

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Autores principales: Peguda, Hari Kumar, Carnt, Nicole A., Gu, Zi, Kumar, Naresh, Willcox, Mark D. P., Kuppusamy, Rajesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782699/
https://www.ncbi.nlm.nih.gov/pubmed/36557630
http://dx.doi.org/10.3390/microorganisms10122377
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author Peguda, Hari Kumar
Carnt, Nicole A.
Gu, Zi
Kumar, Naresh
Willcox, Mark D. P.
Kuppusamy, Rajesh
author_facet Peguda, Hari Kumar
Carnt, Nicole A.
Gu, Zi
Kumar, Naresh
Willcox, Mark D. P.
Kuppusamy, Rajesh
author_sort Peguda, Hari Kumar
collection PubMed
description Acanthamoeba is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of Acanthamoeba keratitis is challenging as Acanthamoeba can encyst from the active form, a trophozoite, into a hibernating cyst that is refractory to antibiotics and difficult to kill; therefore, there is a need for more effective anti-amoebic strategies. In this study, we have evaluated the anti-amoebic activity of the antimicrobial peptide mimic RK-758 against Acanthamoeba castellanii. RK-758 peptidomimetic was subjected to biological assays to investigate its amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects on A. castellanii. The anti-amoebic activity of the peptide mimic RK-758 was compared with chlorhexidine against the Acanthamoeba castellanii ATCC30868 and Acanthamoeba castellanii 044 (a clinical strain) with the concentrations of both ranging from 125 µM down to 7.81 µM. All experiments were performed in duplicate with three independent replicates. The data were represented as mean ± SE and analysed using a two-sample t-test and two-tailed distributions. A p < 0.05 was considered statistically significant. The peptidomimetic RK-758 had anti-Acanthamoeba activity against both trophozoites and cysts in a dose-dependent manner. The RK-758 had amoebicidal and growth inhibitory activities of ≥50% at a concentration between 125 µM and 15.6 µM against the trophozoites of both Acanthamoeba strains. Inhibitory effects on the cyst formation and trophozoite re-emergence from cysts were noted at similar concentrations. Chlorhexidine had 50% activity at 7.81 µM and above against the trophozoites and cysts of both strains. In the haemolysis assay, the RK-758 lysed horse RBCs at concentrations greater than 50 µM whereas lysis occurred at concentrations greater than 125 µM for the chlorhexidine. The peptidomimetic RK-758, therefore, has activity against both the trophozoite and cyst forms of Acanthamoeba and has the potential to be further developed as an anti-microbial agent against Acanthamoeba. RK-758 may also have use as an anti-amoebic disinfectant in contact lens solutions.
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spelling pubmed-97826992022-12-24 The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii Peguda, Hari Kumar Carnt, Nicole A. Gu, Zi Kumar, Naresh Willcox, Mark D. P. Kuppusamy, Rajesh Microorganisms Article Acanthamoeba is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of Acanthamoeba keratitis is challenging as Acanthamoeba can encyst from the active form, a trophozoite, into a hibernating cyst that is refractory to antibiotics and difficult to kill; therefore, there is a need for more effective anti-amoebic strategies. In this study, we have evaluated the anti-amoebic activity of the antimicrobial peptide mimic RK-758 against Acanthamoeba castellanii. RK-758 peptidomimetic was subjected to biological assays to investigate its amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects on A. castellanii. The anti-amoebic activity of the peptide mimic RK-758 was compared with chlorhexidine against the Acanthamoeba castellanii ATCC30868 and Acanthamoeba castellanii 044 (a clinical strain) with the concentrations of both ranging from 125 µM down to 7.81 µM. All experiments were performed in duplicate with three independent replicates. The data were represented as mean ± SE and analysed using a two-sample t-test and two-tailed distributions. A p < 0.05 was considered statistically significant. The peptidomimetic RK-758 had anti-Acanthamoeba activity against both trophozoites and cysts in a dose-dependent manner. The RK-758 had amoebicidal and growth inhibitory activities of ≥50% at a concentration between 125 µM and 15.6 µM against the trophozoites of both Acanthamoeba strains. Inhibitory effects on the cyst formation and trophozoite re-emergence from cysts were noted at similar concentrations. Chlorhexidine had 50% activity at 7.81 µM and above against the trophozoites and cysts of both strains. In the haemolysis assay, the RK-758 lysed horse RBCs at concentrations greater than 50 µM whereas lysis occurred at concentrations greater than 125 µM for the chlorhexidine. The peptidomimetic RK-758, therefore, has activity against both the trophozoite and cyst forms of Acanthamoeba and has the potential to be further developed as an anti-microbial agent against Acanthamoeba. RK-758 may also have use as an anti-amoebic disinfectant in contact lens solutions. MDPI 2022-11-30 /pmc/articles/PMC9782699/ /pubmed/36557630 http://dx.doi.org/10.3390/microorganisms10122377 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Peguda, Hari Kumar
Carnt, Nicole A.
Gu, Zi
Kumar, Naresh
Willcox, Mark D. P.
Kuppusamy, Rajesh
The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title_full The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title_fullStr The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title_full_unstemmed The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title_short The Anti-Amoebic Activity of a Peptidomimetic against Acanthamoeba castellanii
title_sort anti-amoebic activity of a peptidomimetic against acanthamoeba castellanii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782699/
https://www.ncbi.nlm.nih.gov/pubmed/36557630
http://dx.doi.org/10.3390/microorganisms10122377
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