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In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect

Intestinal coccidiosis is a common parasitic disease in livestock, caused by the infection of Eimeria and Cystoisospora parasites, which results in great economic losses to animal husbandry. Triazine compounds, such as toltrazuril and diclazuril, are widely used in the treatment and chemoprophylaxis...

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Autores principales: Zhang, Lei, Zhang, Hongtao, Du, Shiqi, Song, Xingju, Hu, Dandan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179680/
https://www.ncbi.nlm.nih.gov/pubmed/37176073
http://dx.doi.org/10.3390/ijms24098370
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author Zhang, Lei
Zhang, Hongtao
Du, Shiqi
Song, Xingju
Hu, Dandan
author_facet Zhang, Lei
Zhang, Hongtao
Du, Shiqi
Song, Xingju
Hu, Dandan
author_sort Zhang, Lei
collection PubMed
description Intestinal coccidiosis is a common parasitic disease in livestock, caused by the infection of Eimeria and Cystoisospora parasites, which results in great economic losses to animal husbandry. Triazine compounds, such as toltrazuril and diclazuril, are widely used in the treatment and chemoprophylaxis of coccidiosis. Unfortunately, widespread drug resistance has compromised their effectiveness. Most studies have focused on prophylaxis and therapeutics with toltrazuril in flocks, while a comprehensive understanding of how toltrazuril treatment alters the transcriptome of E. tenella remains unknown. In this study, merozoites of E. tenella were treated in vitro with 0.5 μg/mL toltrazuril for 0, 1, 2 and 4 h, respectively. The gene transcription profiles were then compared by high-throughput sequencing. Our results showed that protein hydrolysis genes were significantly upregulated after drug treatment, while cell cycle-related genes were significantly downregulated, suggesting that toltrazuril may affect parasite division. The expression of redox-related genes was upregulated and elevated levels of ROS and autophagosomes were detected in the parasite after toltrazuril treatment, suggesting that toltrazuril may cause oxidative stress to parasite cells and lead to its autophagy. Our results provide basic knowledge of the response of Eimeria genes to toltrazuril and further analysis of the identified transcriptional changes can provide useful information for a better understanding of the mechanism of action of toltrazuril against Eimeria.
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spelling pubmed-101796802023-05-13 In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect Zhang, Lei Zhang, Hongtao Du, Shiqi Song, Xingju Hu, Dandan Int J Mol Sci Article Intestinal coccidiosis is a common parasitic disease in livestock, caused by the infection of Eimeria and Cystoisospora parasites, which results in great economic losses to animal husbandry. Triazine compounds, such as toltrazuril and diclazuril, are widely used in the treatment and chemoprophylaxis of coccidiosis. Unfortunately, widespread drug resistance has compromised their effectiveness. Most studies have focused on prophylaxis and therapeutics with toltrazuril in flocks, while a comprehensive understanding of how toltrazuril treatment alters the transcriptome of E. tenella remains unknown. In this study, merozoites of E. tenella were treated in vitro with 0.5 μg/mL toltrazuril for 0, 1, 2 and 4 h, respectively. The gene transcription profiles were then compared by high-throughput sequencing. Our results showed that protein hydrolysis genes were significantly upregulated after drug treatment, while cell cycle-related genes were significantly downregulated, suggesting that toltrazuril may affect parasite division. The expression of redox-related genes was upregulated and elevated levels of ROS and autophagosomes were detected in the parasite after toltrazuril treatment, suggesting that toltrazuril may cause oxidative stress to parasite cells and lead to its autophagy. Our results provide basic knowledge of the response of Eimeria genes to toltrazuril and further analysis of the identified transcriptional changes can provide useful information for a better understanding of the mechanism of action of toltrazuril against Eimeria. MDPI 2023-05-06 /pmc/articles/PMC10179680/ /pubmed/37176073 http://dx.doi.org/10.3390/ijms24098370 Text en © 2023 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
Zhang, Lei
Zhang, Hongtao
Du, Shiqi
Song, Xingju
Hu, Dandan
In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title_full In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title_fullStr In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title_full_unstemmed In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title_short In Vitro Transcriptional Response of Eimeria tenella to Toltrazuril Reveals That Oxidative Stress and Autophagy Contribute to Its Anticoccidial Effect
title_sort in vitro transcriptional response of eimeria tenella to toltrazuril reveals that oxidative stress and autophagy contribute to its anticoccidial effect
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179680/
https://www.ncbi.nlm.nih.gov/pubmed/37176073
http://dx.doi.org/10.3390/ijms24098370
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