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Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.

Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with a...

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Autores principales: Rodríguez-Expósito, Rubén L., Sifaoui, Ines, Reyes-Batlle, María, Maciver, Sutherland K., Piñero, José E., Lorenzo-Morales, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868517/
https://www.ncbi.nlm.nih.gov/pubmed/35203882
http://dx.doi.org/10.3390/antibiotics11020280
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author Rodríguez-Expósito, Rubén L.
Sifaoui, Ines
Reyes-Batlle, María
Maciver, Sutherland K.
Piñero, José E.
Lorenzo-Morales, Jacob
author_facet Rodríguez-Expósito, Rubén L.
Sifaoui, Ines
Reyes-Batlle, María
Maciver, Sutherland K.
Piñero, José E.
Lorenzo-Morales, Jacob
author_sort Rodríguez-Expósito, Rubén L.
collection PubMed
description Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal activity. The aim of this study was to evaluate the in vitro antiamoebic activity of three third-generation statins—cerivastatin, pitavastatin and rosuvastatin—against both cysts and trophozoites of the following four strains of Acanthamoeba: A. castellanii Neff, A. polyphaga, A. griffini and A. quina. Furthermore, programmed cell death (PCD) induction traits were evaluated by measuring chromatin condensation, damages at the mitochondrial level, production of reactive oxygen species (ROS) and the distribution of actin cytoskeleton fibers. Acanthamoeba castellanii Neff was the strain most sensitive to all the statins, where cerivastatin showed the lowest amoebicidal activity for both trophozoite and cyst forms (0.114 ± 0.050 and 0.704 ± 0.129 µM, respectively). All the statins were able to cause DNA condensation, collapse in the mitochondrial membrane potential and a reduction in ATP level production, and disorganization of the total actin fibers in the cytoskeleton of all the evaluated Acanthamoeba strains. Our results showed that the tested statins were able to induce PCD compatible events in the treated amoebae, including chromatin condensation, collapse in the mitochondrial potential and ATP levels, cytoskeleton disassembly and ROS generation.
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spelling pubmed-88685172022-02-25 Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp. Rodríguez-Expósito, Rubén L. Sifaoui, Ines Reyes-Batlle, María Maciver, Sutherland K. Piñero, José E. Lorenzo-Morales, Jacob Antibiotics (Basel) Article Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal activity. The aim of this study was to evaluate the in vitro antiamoebic activity of three third-generation statins—cerivastatin, pitavastatin and rosuvastatin—against both cysts and trophozoites of the following four strains of Acanthamoeba: A. castellanii Neff, A. polyphaga, A. griffini and A. quina. Furthermore, programmed cell death (PCD) induction traits were evaluated by measuring chromatin condensation, damages at the mitochondrial level, production of reactive oxygen species (ROS) and the distribution of actin cytoskeleton fibers. Acanthamoeba castellanii Neff was the strain most sensitive to all the statins, where cerivastatin showed the lowest amoebicidal activity for both trophozoite and cyst forms (0.114 ± 0.050 and 0.704 ± 0.129 µM, respectively). All the statins were able to cause DNA condensation, collapse in the mitochondrial membrane potential and a reduction in ATP level production, and disorganization of the total actin fibers in the cytoskeleton of all the evaluated Acanthamoeba strains. Our results showed that the tested statins were able to induce PCD compatible events in the treated amoebae, including chromatin condensation, collapse in the mitochondrial potential and ATP levels, cytoskeleton disassembly and ROS generation. MDPI 2022-02-21 /pmc/articles/PMC8868517/ /pubmed/35203882 http://dx.doi.org/10.3390/antibiotics11020280 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
Rodríguez-Expósito, Rubén L.
Sifaoui, Ines
Reyes-Batlle, María
Maciver, Sutherland K.
Piñero, José E.
Lorenzo-Morales, Jacob
Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title_full Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title_fullStr Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title_full_unstemmed Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title_short Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.
title_sort statins induce actin cytoskeleton disassembly and an apoptosis-like process in acanthamoeba spp.
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868517/
https://www.ncbi.nlm.nih.gov/pubmed/35203882
http://dx.doi.org/10.3390/antibiotics11020280
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