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Parasites & Vectors May 2022Schistosomiasis, an acute and chronic parasitic disease, causes substantial morbidity and mortality in tropical and subtropical regions of the world. Iron is an...
BACKGROUND
Schistosomiasis, an acute and chronic parasitic disease, causes substantial morbidity and mortality in tropical and subtropical regions of the world. Iron is an essential constituent of numerous macromolecules involving in important cellular reactions in virtually all organisms. Trematodes of the genus Schistosoma live in iron-rich blood, feed on red blood cells and store abundant iron in vitelline cells. Ferritins are multi-meric proteins that store iron inside cells. Three ferritin isoforms in Schistosoma japonicum are known, namely SjFer0, SjFer1 and SjFer2; however, their impact on the growth and development of the parasites is still unknown. In this study we report on and characterize the ferritins in S. japonicum.
METHODS
A phylogenetic tree of the SjFer0, SjFer1 and SjFer2 genes was constructed to show the evolutionary relationship among species of genus Schistosoma. RNA interference in vivo was used to investigate the impact of SjFer0 on schistosome growth and development. Immunofluorescence assay was applied to localize the expression of the ferritins. RNA-sequencing was performed to characterize the iron transport profile after RNA interference.
RESULTS
SjFer0 was found to have low similarity with SjFer1 and SjFer2 and contain an additional signal peptide sequence. Phylogenetic analysis revealed that SjFer0 can only cluster with some ferritins of other trematodes and tapeworms, suggesting that this ferritin branch might be unique to these parasites. RNA interference in vivo showed that SjFer0 significantly affected the growth and development of schistosomula but did not affect egg production of adult female worms. SjFer1 and SjFer2 had no significant impact on growth and development. The immunofluorescence study showed that SjFer0 was widely expressed in the somatic cells and vitelline glands but not in the testicle or ovary. RNA-sequencing indicated that, in female, the ion transport process and calcium ion binding function were downregulated after SjFer0 RNA interference. Among the differentially downregulated genes, Sj-cpi-2, annexin and insulin-like growth factor-binding protein may be accounted for the suppression of schistosome growth and development.
CONCLUSIONS
The results indicate that SjFer0 affects the growth and development of schistosomula but does not affect egg production of adult female worms. SjFer0 can rescue the growth of the fet3fet4 double mutant Saccharomyces cerevisiae (strain DEY1453), suggesting being able to promote iron absorption. The RNA interference of SjFer0 inferred that the suppression of worm growth and development may via down-regulating Sj-cpi-2, annexin, and IGFBP.
Topics: Animals; Annexins; Female; Ferritins; Growth and Development; Iron; Phylogeny; RNA; Schistosoma japonicum; Schistosomiasis japonica
PubMed: 35610663
DOI: 10.1186/s13071-022-05247-1 -
Frontiers in Cellular and Infection... 2022The microRNA-124-3p plays an important role in regulating development and neurogenesis. Previous microRNA sequencing analyses of revealed sja-miR-124-3p differential...
The microRNA-124-3p plays an important role in regulating development and neurogenesis. Previous microRNA sequencing analyses of revealed sja-miR-124-3p differential expression patterns in schistosomes from different hosts and at different developmental stages. This study explores the regulatory role of sja-miR-124-3p in development and reproduction. Quantitative reverse-transcription PCR (qRT-PCR) showed that the expression level of sja-miR-124-3p in from resistant hosts, such as , and unsuitable hosts, such as rats and water buffalo, was significantly higher than that in mice and yellow cattle at the same developmental stage. Overexpressing sja-miR-124-3p in infected mice led to a hepatic egg reduction rate of 36.97%, smaller egg granulomas in the livers, increased liver weight, subsided hepatocyte necrosis, and diminished inflammatory cell infiltration. The width of female worms increased but decreased in males. The vitelline cells were irregular, swollen, or fused. The teguments and ventral sucker of males and females were swollen and broken, but the morphological changes were particularly notable in males. qRT-PCR and dual-luciferase reporter assay system were used to confirm the -predicted target genes, DEAD-box ATP-dependent RNA helicase 1 () and DNA polymerase II subunit 2 (). Our results showed that RNA interference (RNAi)-mediated silencing in mice provided a 24.55% worm reduction rate and an 18.36% egg reduction rate, but the difference was not significant ( > 0.05). Thus, our findings suggest that sja-miR-124-3p has an important role in growth, development, and reproduction in . All these results will greatly contribute toward providing important clues for searching vaccine candidates and new drug targets against schistosomiasis.
Topics: Animals; Cattle; Female; Liver; Male; Mice; MicroRNAs; RNA Interference; Rats; Reproduction; Schistosoma japonicum
PubMed: 35493736
DOI: 10.3389/fcimb.2022.862496 -
Parasites & Vectors Apr 2019Schistosome parasites lay up to a thousand eggs per day inside the veins of their mammalian hosts. The immature eggs deposited by females against endothelia of venules...
BACKGROUND
Schistosome parasites lay up to a thousand eggs per day inside the veins of their mammalian hosts. The immature eggs deposited by females against endothelia of venules will embryonate within days. Approximately 30% of the eggs will migrate to the lumen of the intestine to continue the parasite life-cycle. Many eggs, however, are trapped in the liver and intestine causing the main pathology associated with schistosomiasis mansoni and japonica, the liver granulomatous response. Excretory-secretory egg proteins drive much of egg-induced pathogenesis of schistosomiasis mansoni, and Schistosoma japonicum induce a markedly distinct granulomatous response to that of S. mansoni.
METHODS
To explore the basis of variations in this responsiveness, we investigated the proteome of eggs of S. japonicum. Using mass spectrometry qualitative and quantitative (SWATH) analyses, we describe the protein composition of S. japonicum eggs secretory proteins (ESP), and the differential expression of proteins by fully mature and immature eggs, isolated from faeces and ex vivo adults.
RESULTS
Of 957 egg-related proteins identified, 95 were exclusively found in S. japonicum ESP which imply that they are accessible to host immune system effector elements. An in-silico analysis implies that ESP are able of stimulating the innate and adaptive immune system through several different pathways. While quantitative SWATH analysis revealed 124 proteins that are differentially expressed by mature and immature S. japonicum eggs, illuminating some important aspects of eggs biology and infection, we also show that mature eggs are more likely than immature eggs to stimulate host immune responses.
CONCLUSIONS
Here we present a list of potential targets that can be used to develop better strategies to avoid severe morbidity during S. japonicum infection, as well as improving diagnosis, treatment and control of schistosomiasis japonica.
Topics: Animals; Cell Survival; Egg Proteins; Female; Gene Expression Profiling; Helminth Proteins; Mice; Ovum; Proteome; Schistosoma japonicum
PubMed: 30992086
DOI: 10.1186/s13071-019-3403-1 -
Acta Tropica Aug 2022The co-evolution of Schistosoma and its host necessitates the use of extracellular vesicles (EVs) generated by different lifecycle stages to manipulate the host immune... (Review)
Review
The co-evolution of Schistosoma and its host necessitates the use of extracellular vesicles (EVs) generated by different lifecycle stages to manipulate the host immune system to achieve a delicate balance between the survival of the parasite and the limited pathology of the host. EVs are phospholipid bilayer membrane-enclosed vesicles capable of transferring a complex mixture of proteins, lipids, and genetic materials to the host. They are nano-scale-sized vesicles involved in cellular communication. In this review, the author summarized the proteins involved in the biogenesis of schistosome-derived EVs and their cargo load. miRNAs are one cargo molecule that can underpin EVs functions and significantly affect parasite/host interactions and immune modulation. They skew macrophage polarization towards the M1 phenotype and downregulate Th2 immunity. Schistosoma can evade the host immune system's harmful effects by utilizing this strategy. In order to compromise the protective effect of Th2, EVs upregulate T regulatory cells and activate eosinophils, which contribute to granuloma formation. Schistosomal EVs also affect fibrosis by acting on non-immune cells such as hepatic stellate cells. These vesicles drew attention to translational applications in diagnosis, immunotherapy, and potential vaccines. A deep understanding of the interaction of schistosome-derived EVs with host cells will significantly increase our knowledge about the dynamics between the host and the worm that may aid in controlling this debilitating disease.
Topics: Animals; Extracellular Vesicles; Host-Parasite Interactions; MicroRNAs; Proteomics; Schistosoma japonicum
PubMed: 35427535
DOI: 10.1016/j.actatropica.2022.106467 -
Parasites & Vectors Nov 2022Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of...
BACKGROUND
Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of transition from chronic to advanced S. japonicum infection remains largely unknown. Evidences suggested that gut microbiota plays a role in the pathogenesis of S. japonicum infection. However, the composition of the gut microbiota in patients with chronic and advanced S. japonicum infection is not well defined. In this study, we compared the composition of the intestinal flora in patients with chronic and advanced S. japonicum infection.
METHODS
The feces of 24 patients with chronic S. japonicum infection and five patients with advanced S. japonicum infection from the same area were collected according to standard procedures, and 16S rRNA sequencing technology was used to analyze the intestinal microbial composition of the two groups of patients.
RESULTS
We found that alteration occurs in the gut microbiota between the groups of patients with chronic and advanced S. japonicum infections. Analysis of alpha and beta diversity indicated that the diversity and abundance of intestinal flora in patients with advanced S. japonicum infection were lower than those in patients with chronic S. japonicum infection. Furthermore, Prevotella 9, Subdoligranulum, Ruminococcus torques, Megamonas and Fusicatenibacter seemed to have potential to discriminate different stages of S. japonicum infection and to act as biomarkers for diagnosis. Function prediction analysis revealed that microbiota function in the chronic group was focused on translation and cell growth and death, while that in the advanced group was concentrated on elevating metabolism-related functions.
CONCLUSIONS
Our study demonstrated that alteration in gut microbiota in different stages of S. japonicum infection plays a potential role in the pathogenesis of transition from chronic to advanced S. japonicum infection. However, further validation in the clinic is needed, and the underlying mechanism requires further study.
Topics: Humans; Animals; Schistosomiasis japonica; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Intestines; Schistosoma japonicum
PubMed: 36345042
DOI: 10.1186/s13071-022-05539-6 -
International Journal For Parasitology.... Aug 2020Human schistosomiasis is a disease which globally affects over 229 million people. Three major species affecting humans are Schistosoma mansoni, S. haematobium and S....
Human schistosomiasis is a disease which globally affects over 229 million people. Three major species affecting humans are Schistosoma mansoni, S. haematobium and S. japonicum. Previous treatment of S. mansoni includes the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The OXA activating enzyme was identified and crystallized, as being a S. mansoni sulfotransferase (SmSULT). S. haematobium and S. japonicum possess homologs of SmSULT (ShSULT and SjSULT) begging the question; why does oxamniquine fail to kill S. haematobium and S. japonicum adult worms? Investigation of the molecular structures of the sulfotransferases indicates that structural differences, specifically in OXA contact residues, do not abrogate OXA binding in the active sites as previously hypothesized. Data presented argue that the ability of SULTs to sulfate and thus activate OXA and its derivatives is linked to the ability of OXA to fit in the binding pocket to allow the transfer of a sulfur group.
Topics: Animals; Molecular Structure; Oxamniquine; Schistosoma; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomicides; Sulfotransferases
PubMed: 32315953
DOI: 10.1016/j.ijpddr.2020.04.001 -
Biochemical and Biophysical Research... May 2022Schistosoma japonicum is a parasitic worm that lives in the mesenteric vein of its host and feeds on blood, suggesting that it might be a natural resource of novel...
Schistosoma japonicum is a parasitic worm that lives in the mesenteric vein of its host and feeds on blood, suggesting that it might be a natural resource of novel anticoagulants. Here, by comprehensive analyses of the genomic sequences of Schistosoma japonicum, a new Kunitz-type gene precursor was identified. The Kunitz-type gene precursor codes for an 18-residue signal peptide and a 60-residue mature peptide. The Kunitz peptide was functionally expressed, and it had apparent inhibitory activity towards the intrinsic coagulation pathway but no effect on the extrinsic coagulation pathway even at the high concentration of 3 μM. Enzyme and inhibitor experiments further showed that the Kunitz domain peptide was a potent and selective FXa inhibitor, so it was named Schixator (Schistosoma FXa inhibitor). Schixator inhibits coagulation factor FXa with a Ki of 2.66 nM, but had weak inhibitory activity towards chymotrypsin, FXIa, plasma kallikrein, and plasmin, and no inhibitory activity towards trypsin, elastase, FIIa or FXIIa. In vivo, the intravenous administration of Schixator into mice dramatically decreased the number of thrombi in the carotid artery in an FeCl-induced thrombus formation model without producing bleeding complications. To the best of our knowledge, Schixator is the first potent and selective FXa inhibitor from parasitic worms with antithrombotic effects and a low bleeding risk that provides a new clue for lead drug discovery against thrombosis-associated human diseases.
Topics: Animals; Anticoagulants; Blood Coagulation; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Mice; Schistosoma japonicum; Thrombosis
PubMed: 35287055
DOI: 10.1016/j.bbrc.2022.03.005 -
Acta Tropica Feb 2019The exact impact of climate change on schistosomiasis, a disease caused by a blood fluke that affects more than 250 million people mainly in tropical and subtropical... (Review)
Review
The exact impact of climate change on schistosomiasis, a disease caused by a blood fluke that affects more than 250 million people mainly in tropical and subtropical countries, is currently unknown, but likely to vary with the snail-parasite species' specific ecologies and the spatio-temporal scale of investigation. Here, by means of a systematic review to identify studies reporting on impacts of climate change on the agents of schistosomiasis, we provide an updated synthesis of the current knowledge about the climate change-schistosomiasis relation. We found that, despite a recent increase in scientific studies that discuss the potential impact of climate change on schistosomiasis, only a handful of reports have applied modelling and predictive forecasting that provide a quantitative estimate of potential outcomes. The volume and type of evidence associated with climate change responses were found to be variable across geographical regions and snail-parasite taxonomic groups. Indeed, the strongest evidence stems from the People's Republic of China pertaining to Schistosoma japonicum. Some evidence is also available from eastern Africa, mainly for Schistosoma mansoni. While studies focused on the northern and southern range margins for schistosomiasis indicate an increase in transmission range as the most likely outcome, there was less agreement about the direction of outcomes from the central and eastern parts of Africa. The current lack of consensus suggests that climate change is more likely to shift than to expand the geographic ranges of schistosomiasis. A comparison between the current geographical distributions and the thermo-physiological limitations of the two main African schistosome species (Schistosoma haematobium and S. mansoni) offered additional insights, and showed that both species already exist near their thermo-physiological niche boundaries. The African species both stand to move considerably out of their "thermal comfort zone" in a future, warmer Africa, but S. haematobium in particular is likely to experience less favourable climatic temperatures. The consequences for schistosomiasis transmission will, to a large extent, depend on the parasites and snails ability to adapt or move. Based on the identified geographical trends and knowledge gaps about the climate change-schistosomiasis relation, we propose to align efforts to close the current knowledge gaps and focus on areas considered to be the most vulnerable to climate change.
Topics: Animals; Climate Change; Humans; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Snails
PubMed: 30261186
DOI: 10.1016/j.actatropica.2018.09.013 -
Parasites & Vectors Dec 2023Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease... (Review)
Review
Exploring the immune interactions between Oncomelania hupensis and Schistosoma japonicum, with a cross-comparison of immunological research progress in other intermediate host snails.
Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of "neglected tropical disease". Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host's immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms.
Topics: Animals; Humans; Schistosoma japonicum; Schistosomiasis; Biomphalaria; Bulinus; Schistosoma mansoni
PubMed: 38093363
DOI: 10.1186/s13071-023-06011-9 -
Parasites & Vectors Feb 2017The blood fluke, Schistosoma japonicum still causes severe disease in China, the Philippines and Indonesia. Although there have been some studies the molecular...
BACKGROUND
The blood fluke, Schistosoma japonicum still causes severe disease in China, the Philippines and Indonesia. Although there have been some studies the molecular epidemiology of this persistent and harmful parasite, few have explored the possibility and implications of selection in S. japonicum populations.
METHODS
We analyzed diversity and looked for evidence of selection at three nuclear genes (SjIpp2, SjFabp and SjT22.6) in 13 S. japonicum populations.
RESULTS
SjT22.6 was found to exhibit high nucleotide diversity and was under positive selection in the mountainous region of mainland China. As a tegumental protein, its secondary and tertiary structure differed between S. japonicum strains from the mountainous and lakes regions. In contrast, SjIpp2 and SjFabp had relatively low levels of nucleotide diversity and did not show significant departure from neutrality.
CONCLUSIONS
As a tegument-associated antigen-encoding gene of S. japonicum, SjT22.6 has high nucleotide diversity and appears to be under positive selection in the mountainous region of mainland China.
Topics: Animals; Antigens, Helminth; China; Genes, Helminth; Genetic Variation; Schistosoma japonicum; Schistosomiasis japonica; Selection, Genetic; Sequence Analysis, DNA
PubMed: 28212676
DOI: 10.1186/s13071-017-2033-8