The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i>
<i>Acanthamoeba </i>is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of <i>Acanthamoeba</i> keratitis is challenging as <i>Acanthamoeba</i> can encyst from the active form, a trophozoite, into a hi...
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MDPI AG
2022-11-01
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author | Hari Kumar Peguda Nicole A. Carnt Zi Gu Naresh Kumar Mark D. P. Willcox Rajesh Kuppusamy |
author_facet | Hari Kumar Peguda Nicole A. Carnt Zi Gu Naresh Kumar Mark D. P. Willcox Rajesh Kuppusamy |
author_sort | Hari Kumar Peguda |
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description | <i>Acanthamoeba </i>is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of <i>Acanthamoeba</i> keratitis is challenging as <i>Acanthamoeba</i> 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 <i>Acanthamoeba castellanii</i>. RK-758 peptidomimetic was subjected to biological assays to investigate its amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects on <i>A. castellanii</i>. The anti-amoebic activity of the peptide mimic RK-758 was compared with chlorhexidine against the <i>Acanthamoeba castellanii </i>ATCC30868 and <i>Acanthamoeba castellanii </i>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 <i>t</i>-test and two-tailed distributions. A <i>p </i>< 0.05 was considered statistically significant. The peptidomimetic RK-758 had anti-<i>Acanthamoeba</i> 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 <i>Acanthamoeba </i>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 <i>Acanthamoeba</i> and has the potential to be further developed as an anti-microbial agent against <i>Acanthamoeba</i>. RK-758 may also have use as an anti-amoebic disinfectant in contact lens solutions. |
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spelling | doaj.art-a48fd96ef2dc40eb8f408087d6344bf12023-11-24T16:48:04ZengMDPI AGMicroorganisms2076-26072022-11-011012237710.3390/microorganisms10122377The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i>Hari Kumar Peguda0Nicole A. Carnt1Zi Gu2Naresh Kumar3Mark D. P. Willcox4Rajesh Kuppusamy5School of Optometry and Vision Science, University of New South Wales, Sydney 2052, AustraliaSchool of Optometry and Vision Science, University of New South Wales, Sydney 2052, AustraliaSchool of Chemical Engineering, University of New South Wales, Sydney 2052, AustraliaSchool of Chemistry, University of New South Wales, Sydney 2052, AustraliaSchool of Optometry and Vision Science, University of New South Wales, Sydney 2052, AustraliaSchool of Optometry and Vision Science, University of New South Wales, Sydney 2052, Australia<i>Acanthamoeba </i>is a free-living protozoan known to cause keratitis most commonly, especially among contact lens wearers. Treatment of <i>Acanthamoeba</i> keratitis is challenging as <i>Acanthamoeba</i> 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 <i>Acanthamoeba castellanii</i>. RK-758 peptidomimetic was subjected to biological assays to investigate its amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects on <i>A. castellanii</i>. The anti-amoebic activity of the peptide mimic RK-758 was compared with chlorhexidine against the <i>Acanthamoeba castellanii </i>ATCC30868 and <i>Acanthamoeba castellanii </i>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 <i>t</i>-test and two-tailed distributions. A <i>p </i>< 0.05 was considered statistically significant. The peptidomimetic RK-758 had anti-<i>Acanthamoeba</i> 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 <i>Acanthamoeba </i>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 <i>Acanthamoeba</i> and has the potential to be further developed as an anti-microbial agent against <i>Acanthamoeba</i>. RK-758 may also have use as an anti-amoebic disinfectant in contact lens solutions.https://www.mdpi.com/2076-2607/10/12/2377<i>Acanthamoeba</i>free-living amoebaanti-microbial peptidespeptidomimetics |
spellingShingle | Hari Kumar Peguda Nicole A. Carnt Zi Gu Naresh Kumar Mark D. P. Willcox Rajesh Kuppusamy The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> Microorganisms <i>Acanthamoeba</i> free-living amoeba anti-microbial peptides peptidomimetics |
title | The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> |
title_full | The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> |
title_fullStr | The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> |
title_full_unstemmed | The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> |
title_short | The Anti-Amoebic Activity of a Peptidomimetic against <i>Acanthamoeba castellanii</i> |
title_sort | anti amoebic activity of a peptidomimetic against i acanthamoeba castellanii i |
topic | <i>Acanthamoeba</i> free-living amoeba anti-microbial peptides peptidomimetics |
url | https://www.mdpi.com/2076-2607/10/12/2377 |
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