Project description:Exploration of the whole mitochondrial genetic polymorphism of Echinococcus multilocularis in French alveolar echinococcosis patients
Project description:We used a mouse model of alveolar echinococcosis to assess gene expression profiles in the liver after establishment of a chronic disease status as a result of a primary peroral infection with eggs of the fox tapeworm Echinococcus multilocularis.
Project description:The cestodes Echinococcus granulosus and Echinococcus multilocularis, as the pathogens of cystic echinococcosis and alveolar echinococcosis respectively, can cause significant health problems to the host and considerable socio-economic losses as a consequence. Based on the genomic data regarding these two species available in public database recently, we carried out high-throughput mRNA and small RNA transcriptomic sequencing of them and generate enormous transcriptomic datasets. A total of 34,717,856 reads (79.79%) mapped to E. granulosus genome, and 38,882,179 reads (87.61%) mapped to E. multiloculari genome. A total of 24,550 (7,925 known and 16,625 novel transcripts) and 23,771 transcripts (8,432 known and 15,339 novel transcripts) were assembled for E. granulosus and E. multilocularis respectively, and the assembly yielded 11,330 genes (6,815 known and 4,515 novel genes) for E. granulosus and 10,101 genes (7,051 known and 3,050 novel genes) for E. multilocularis, compared with the reference genome data. Bioinformatic analysis identified 6,826 AS events from 3,774 E. granulosus genes (33.31%) and 6,644 AS events in 3,611 E. multilocularis genes (35.75%). A total of 76,674 distinct microRNAs of E. granulosus and 115,742 of E. multilocularis were also obtained from small RNA transcriptome sequencing reads. Of these, there were 20 microRNAs of E. granulosus and 22 microRNAs of E. multilocularis that belonged to 19 and 21 microRNA families common to other metazoan lineages separately. 76 and 90 novel microRNAs so far unique to E. granulosus and E. multilocularis were also identified respectively. This study represents an extensive mRNA and small RNA transcriptome dataset obtained from the deep sequencing of these two cestode species. The findings will facilitate a more fundamental understanding of cestode biology, evolution, the host-parasite interplay, and provide new insights into the pathophysiology of echinococcosis, contributing to the development of improved interventions for disease control.
Project description:Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, supported by serology and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers of several diseases. Here, we profiled the sRNA transcriptomes in the context of AE and CE to identify novel biomarkers to aid in medical decisions. For this, endogenous and parasitic sRNAs were analysed by sRNA sequencing in sera from disease negative, positive, and treated patients and patients harbouring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE and/or non-parasitic liver lesion were identified. Our results represent an in-depth characterisation of the effect E. multilocularis and E. granulosus s.l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.
Project description:<h4><strong>BACKGROUND:</strong> Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance (<sup>1</sup>H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE.</h4><h4><strong>RESULTS: </strong>A total of 21 distinct metabolic differences between HAE patients and healthy individuals were identified, and they are associated with perturbations in amino acid metabolism, energy metabolism, glyoxylate and dicarboxylate metabolism. Furthermore, the present results showed that the Fischer ratio, which is the molar ratio of branched-chain amino acids to aromatic amino acids, was significantly lower (P < 0.001) in the blood serum obtained from the HAE patients than it was in the healthy patient group.</h4><h4><strong>CONCLUSIONS: </strong>The altered Fischer ratio, together with perturbations in metabolic pathways identified in the present study, may provide new insights into the mechanistic understanding of HAE pathogenesis and potential therapeutic interventions.</h4>
Project description:Hepatic echinococcosis (HE) caused by Echinococcus spp. transmitted from carnivores is known as a severe zoonotic disease that formed into hepatic cystic echinococcosis (HCE) and hepatic alveolar echinococcosis (HAE). It continues to be a serious public health issue around the world. HAE is uncommon infection which is characterized by poor prognosis but it is the most life-threatening compare to HCE. Many cases of HAE are recognized at forward stages because clinical symptoms may remain silent in about 10 years of incubation period. Several pathological cases could be observed including septicemia, abscess, recurrent cholangitis, and portal hypertensive gastrointestinal bleeding in untreated people. It is provided that correlated factors includes CD44, Soluble ST2 (sST2), Plasma IL-23, IL-27, and IL-5 for metastasis and prognosis for patients with HAE were identified. However, data on metastatic and prognostic marker are still so poor. Recent studies have revealed that circRNAs are enriched and stable in exosomes. Exosomal circRNAs may be localized in platelet-derived extracellular vesicles, hepatic cells, and pancreatic cancer cells. Studies have suggested that it is possible that cells may transfer circRNAs by excreting them in exosomes. Whereas there are a lot of studies on cancer and other human diseases related exosomal circRNA, no studies on hepatic alveolar echinococcosis-related exosomal circRNAs in humans. Current study provides that exosomal circular RNAs from healthy humans and humans with hepatic alveolar echinococcal disease were detected and characterized using the RNA sequencing.
Project description:The larval stage of the cestode Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal disease if untreated. To date, drug treatment options are limited, non-curative and need improvement. In this project we investigated the proteomic composition of in vitro generated metacestodes that are the disease-causing stage of the parasite. We analysed the composition of the vesicle tissue (VT), the vesicle fluid (VF), as well as the changes in the surrounding culture medium (CM). Further we compared the composition of VF ex vivo material from infected mice. As antigen B (AgB) subunits were the most prominent proteins in both VFs and CM, we followed up on these specific proteins and assessed the possibility of re-uptake of AgB into the metacestode, by targeted proteomics against HA-tagged AgB.Six proteomic analyses were performed:1_ VF and VT 2_ CM (in vitro samples)3_ VF ex vivo samples from infected mice4_ HA-AgB8 calibration (in vitro samples)5_ HA-AgB8/1 uptake (in vitro samples)6_ HA-AgB8/2 uptake (in vitro samples)
Project description:For Samples GSM601017-28: The aim of this study was to use expression profiling to define transcriptional patterns and regulatory pathways that characterize the host liver response to E. multilocularis infection in the experimental model of secondary infection, to compare gene expression in this model to those described in the model of "primary infection", and to follow the changes in gene expression and in the expression of a cell proliferation marker over time during the complete chronic phase of E.multilocularis infection, following early and middle stages. For Samples GSM601029-40: The aim of this study was to use expression profiling to define transcriptional patterns and regulatory pathways that characterize the host liver response to E. multilocularis infection in the experimental model of secondary infection, to compare gene expression in this model to those described in the model of "primary infection", and to follow the changes in gene expression and in the expression of a cell proliferation marker over time during the complete chronic phase of E.multilocularis infection, following its middle and late stages. For Samples GSM601017-28: The anterior liver tissue sample of control mice group and alveolar echinococcosis mice group were obtained at each time point(1 month and 3 month). Biological replicates is 3. Then, total RNA from anterior liver of both groups were used as test sample, which labelled cy5 fluorescein, and the pool RNA of healthy BALB/c mice anterior liver was used as reference sample, which labelled cy3 fluorescein, and then hybridized to 32K Mouse Genome Array Genechips, representing about 25000 characterized murine genes. For Samples GSM601029-40: The anterior liver tissue sample of control mice group and alveolar echinococcosis mice group were obtained at each time point(2 month and 6 month). Biological replicates is 3. Then, total RNA from anterior liver of both groups were used as test sample, which labelled cy5 fluorescein, and the pool RNA of healthy BALB/c mice anterior liver was used as reference sample, which labelled cy3 fluorescein, and then hybridized to 36K Mouse Genome Array Genechips, representing about 25000 characterized murine genes.