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 co...
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doaj-efe28e7f524b45858689fa1a1940f1912020-11-25T02:06:01ZengBMCParasites & Vectors1756-33052020-02-0113111110.1186/s13071-020-3970-1Transcriptional changes in Toxoplasma gondii in response to treatment with monensinBintao Zhai0Jun-Jun He1Hany M. Elsheikha2Jie-Xi Li3Xing-Quan Zhu4Xiaoye Yang5College of Veterinary Medicine, Inner Mongolia Agricultural UniversityState Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesFaculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of NottinghamState Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityBackground 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.http://link.springer.com/article/10.1186/s13071-020-3970-1Toxoplasma gondiiMonensinPK-15 cellsRNA-sequencing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bintao Zhai Jun-Jun He Hany M. Elsheikha Jie-Xi Li Xing-Quan Zhu Xiaoye Yang |
spellingShingle |
Bintao Zhai Jun-Jun He Hany M. Elsheikha Jie-Xi Li Xing-Quan Zhu Xiaoye Yang Transcriptional changes in Toxoplasma gondii in response to treatment with monensin Parasites & Vectors Toxoplasma gondii Monensin PK-15 cells RNA-sequencing |
author_facet |
Bintao Zhai Jun-Jun He Hany M. Elsheikha Jie-Xi Li Xing-Quan Zhu Xiaoye Yang |
author_sort |
Bintao Zhai |
title |
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_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_sort |
transcriptional changes in toxoplasma gondii in response to treatment with monensin |
publisher |
BMC |
series |
Parasites & Vectors |
issn |
1756-3305 |
publishDate |
2020-02-01 |
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. |
topic |
Toxoplasma gondii Monensin PK-15 cells RNA-sequencing |
url |
http://link.springer.com/article/10.1186/s13071-020-3970-1 |
work_keys_str_mv |
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