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Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

BACKGROUND: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the c...

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Autores principales: Zhai, Bintao, He, Jun-Jun, Elsheikha, Hany M., Li, Jie-Xi, Zhu, Xing-Quan, Yang, Xiaoye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029487/
https://www.ncbi.nlm.nih.gov/pubmed/32070423
http://dx.doi.org/10.1186/s13071-020-3970-1
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author Zhai, Bintao
He, Jun-Jun
Elsheikha, Hany M.
Li, Jie-Xi
Zhu, Xing-Quan
Yang, Xiaoye
author_facet Zhai, Bintao
He, Jun-Jun
Elsheikha, Hany M.
Li, Jie-Xi
Zhu, Xing-Quan
Yang, Xiaoye
author_sort Zhai, Bintao
collection PubMed
description BACKGROUND: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii. METHODS: Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 μM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis. RESULTS: A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation. CONCLUSIONS: Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii. [Image: see text]
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spelling pubmed-70294872020-02-25 Transcriptional changes in Toxoplasma gondii in response to treatment with monensin Zhai, Bintao He, Jun-Jun Elsheikha, Hany M. Li, Jie-Xi Zhu, Xing-Quan Yang, Xiaoye Parasit Vectors Research BACKGROUND: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii. METHODS: Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 μM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis. RESULTS: A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation. CONCLUSIONS: Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii. [Image: see text] BioMed Central 2020-02-18 /pmc/articles/PMC7029487/ /pubmed/32070423 http://dx.doi.org/10.1186/s13071-020-3970-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhai, Bintao
He, Jun-Jun
Elsheikha, Hany M.
Li, Jie-Xi
Zhu, Xing-Quan
Yang, Xiaoye
Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title_full Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title_fullStr Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title_full_unstemmed Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title_short Transcriptional changes in Toxoplasma gondii in response to treatment with monensin
title_sort transcriptional changes in toxoplasma gondii in response to treatment with monensin
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029487/
https://www.ncbi.nlm.nih.gov/pubmed/32070423
http://dx.doi.org/10.1186/s13071-020-3970-1
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