Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine

Yon, YU; Li, Jun; Wang, Weisi; Qi, Wenjing; Zheng, Xiao; Duan, Lei; Chen, Jiaxu; Li, Shi-Zhu; Han, Xiumin; Zhang, Wenbao; Duan, Liping

doi:10.1186/s12864-021-07875-w

Cited by 5 publications

(5 citation statements)

References 45 publications

(55 reference statements)

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“…Purine is involved in DNA and RNA functions and is essential for cell survival and proliferation ( Pedley and Benkovic, 2017 ). Heat stress will lead to oxidative stress in organisms, and purine metabolism is the basic reaction of oxidative stress and the imbalance between purine remedy and de novo synthesis pathway will lead to the production of ROS ( Yu et al, 2021 ; Tian et al, 2022 ). Besides, the metabolism of intestinal microorganisms will affect the content change of metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the differential pathway of microbial function prediction also includes purine metabolism, which also explains why it is enriched in metabolome data. ABC transporter is a transmembrane protein that can transport many molecules across the cell membrane ( Yu et al, 2021 ). As a member of the ABC transporters, ABCB10 deficiency may lead to mitochondrial oxidative damage and ROS production ( Liesa et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

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Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

Liu,

Ma,

Wang

et al. 2023

Front. Microbiol.

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IntroductionHeat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them.MethodsThus, at 28 days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28–42 days, the HS was kept at 31 ± 1°C (9:00–17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance (n = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment.Results and discussionThe results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of p < 0.05). Transcriptome KEGG enrichment showed that the differential genes were mainly enriched in the NF-kB signaling pathway. Metabolomics results showed that KEGG enrichment showed that the differential metabolites were mainly enriched in the mTOR signaling pathway. 16S rDNA amplicon sequencing results indicated that heat stress increased the relative abundance of Proteobacteria decreased the relative abundance of Firmicutes. Multi-omics analysis showed that the co-participating pathway of differential genes, metabolites and microorganisms KEGG enrichment was purine metabolism. Pearson correlation analysis found that ornithine was positively correlated with SULT1C3, GSTT1L and g_Lactobacillus, and negatively correlated with CALB1. PE was negatively correlated with CALB1 and CHAC1, and positively with g_Alistipes. In conclusion, heat stress can generate large amounts of reactive oxygen and increase the types of harmful bacteria, reduce intestinal nutrient absorption and antioxidant capacity, and thereby damage intestinal health and immune function, and reduce growth performance indicators. This biological process is manifested in the complex regulation, providing a foundational theoretical basis for solving the problem of heat stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

Liu,

Ma,

Wang

et al. 2023

Front. Microbiol.

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“…Other studies addressed the general protein encoding transcriptomic profiles of larvae and/or adult worms of H. microstoma ( Olson et al., 2018 ; Preza et al., 2021 ), Mesocestoides corti ( Basika et al., 2019 ), Sparganum proliferum ( Kikuchi et al., 2021 ), Dibothriocephalus dendriticus ( Sidorova et al., 2023 ), Taenia pisiformis ( Zhang, 2019 ), and T. multiceps ( Li et al., 2017 ). In Echinococcus , transcriptomic studies so far concentrated on E. multilocularis oncospheres ( Huang et al., 2016 ), on different aspects of E. granulosus protoscoleces ( Liu et al., 2017 ; Fan et al., 2020 ; Mohammadi et al., 2021 ; Yu et al., 2021 ; Pereira et al., 2022 ), or on the effects of electroporation on early E. multilocularis primary cell cultures ( Pérez et al., 2022 ). However, none of these studies aimed at identifying the gene expression profiles of specific Echinococcus cell types.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Herz,

Zarowiecki,

Wessels

et al. 2024

Front. Cell. Infect. Microbiol.

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The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage of the tapeworm Echinococcus multilocularis within host organs. We previously demonstrated that metacestode proliferation is exclusively driven by somatic stem cells (germinative cells), which are the only mitotically active parasite cells that give rise to all differentiated cell types. The Echinococcus gene repertoire required for germinative cell maintenance and differentiation has not been characterised so far. We herein carried out Illumina sequencing on cDNA from Echinococcus metacestode vesicles, from metacestode tissue depleted of germinative cells, and from Echinococcus primary cell cultures. We identified a set of ~1,180 genes associated with germinative cells, which contained numerous known stem cell markers alongside genes involved in replication, cell cycle regulation, mitosis, meiosis, epigenetic modification, and nucleotide metabolism. Interestingly, we also identified 44 stem cell associated transcription factors that are likely involved in regulating germinative cell differentiation and/or pluripotency. By in situ hybridization and pulse-chase experiments, we also found a new general Echinococcus stem cell marker, EmCIP2Ah, and we provide evidence implying the presence of a slow cycling stem cell sub-population expressing the extracellular matrix factor Emkal1. RNA-Seq analyses on primary cell cultures revealed that metacestode-derived Echinococcus stem cells display an expanded differentiation capability and do not only form differentiated cell types of the metacestode, but also cells expressing genes specific for protoscoleces, adult worms, and oncospheres, including an ortholog of the schistosome praziquantel target, EmTRPMPZQ. Finally, we show that primary cell cultures contain a cell population expressing an ortholog of the tumour necrosis factor α receptor family and that mammalian TNFα accelerates the development of metacestode vesicles from germinative cells. Taken together, our analyses provide a robust and comprehensive characterization of the Echinococcus germinative cell transcriptome, demonstrate expanded differentiation capability of metacestode derived stem cells, and underscore the potential of primary germinative cell cultures to investigate developmental processes of the parasite. These data are relevant for studies into the role of Echinococcus stem cells in parasite development and will facilitate the design of anti-parasitic drugs that specifically act on the parasite germinative cell compartment.

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“…Recently, transcriptome sequencing has provided an excellent tool to dissect the differentially expressed genes (DEGs) between different research conditions, which could supply global and important information reflecting the influence of one or more inducements on the target cells or tissues at the transcriptional level [ 25 ]. Therefore, the present study aims to reveal the changes in gene expression of T. vaginalis in response to MTZ at an early stage after MTZ treatment but before T. vaginalis widely dies depending on RNA-seq.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profile of Trichomonas vaginalis in response to metronidazole

Xie¹,

Zhong²,

Guan³

et al. 2023

BMC Genomics

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Background Trichomoniasis caused by Trichomonas vaginalis, combined with its complications, has long frequently damaged millions of human health. Metronidazole (MTZ) is the first choice for therapy. Therefore, a better understanding of its trichomonacidal process to ultimately reveal the global mechanism of action is indispensable. To take a step toward this goal, electron microscopy and RNA sequencing were performed to fully reveal the early changes in T. vaginalis at the cellular and transcriptome levels after treatment with MTZ in vitro. Results The results showed that the morphology and subcellular structures of T. vaginalis underwent prominent alterations, characterized by a rough surface with bubbly protrusions, broken holes and deformed nuclei with decreased nuclear membranes, chromatin and organelles. The RNA-seq data revealed a total of 10,937 differentially expressed genes (DEGs), consisting of 4,978 upregulated and 5,959 downregulated genes. Most DEGs for the known MTZ activators, such as pyruvate:ferredoxin oxidoreductase (PFOR) and iron-sulfur binding domain, were significantly downregulated. However, genes for other possible alternative MTZ activators such as thioredoxin reductase, nitroreductase family proteins and flavodoxin-like fold family proteins, were dramatically stimulated. GO and KEGG analyses revealed that genes for basic vital activities, proteostasis, replication and repair were stimulated under MTZ stress, but those for DNA synthesis, more complicated life activities such as the cell cycle, motility, signaling and even virulence were significantly inhibited in T. vaginalis. Meanwhile, increased single nucleotide polymorphism (SNP) and insertions - deletions (indels) were stimulated by MTZ. Conclusions The current study reveals evident nuclear and cytomembrane damage and multiple variations in T. vaginalis at the transcriptional level. These data will offer a meaningful foundation for a deeper understanding of the MTZ trichomonacidal process and the transcriptional response of T. vaginalis to MTZ-induced stress or even cell death.

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Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine

Cited by 5 publications

References 45 publications

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Transcriptional profile of Trichomonas vaginalis in response to metronidazole

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