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Microbiology Spectrum Apr 2024Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as...
UNLABELLED
Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic has been shown to alleviate the pathological injuries in mice infected with by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in infected mice treated with . The results revealed that intervention with altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of and genes translated to urease was significantly restored. Further analysis showed that was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica.
IMPORTANCE
Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with and significant increase in the abundance of beneficial bacteria after the intervention of . At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.
Topics: Animals; Mice; Schistosomiasis japonica; Gastrointestinal Microbiome; Bacillus amyloliquefaciens; Urease; Schistosoma japonicum; Bacteria
PubMed: 38441977
DOI: 10.1128/spectrum.03735-23 -
Animals : An Open Access Journal From... Sep 2023The prevalence of schistosomiasis japonica in China is now characterized by a low epidemic rate and low-intensity infections. Some diagnostic methods with high...
The prevalence of schistosomiasis japonica in China is now characterized by a low epidemic rate and low-intensity infections. Some diagnostic methods with high sensitivity and specificity are urgently needed to better monitor this disease in the current situation. In this study, the detection efficacy of a real-time fluorescent quantitative PCR (qPCR) assay was assessed for schistosomiasis japonica in mice, and before and after treatment with praziquantel (PZQ). Our results showed that the sensitivity of the qPCR was 99.3% (152/153, 95% CI: 96.41-99.98%) and its specificity was 100% (77/77, 95% CI: 95.32-100%) in mice infected with different numbers of After the oral administration of PZQ, mice infected with 10 cercariae or 40 cercariae were all -negative 6 weeks after treatment. However, the negativity rates on a soluble egg antigen (SEA)-based enzyme-linked immunosorbent assay (ELISA) were only 34.8% (8/23, 10 cercariae group) and 6.7% (1/15, 40 cercariae group) at the sixth week after PZQ treatment. These results demonstrated that the qPCR method had good sensitivity and specificity, and suggested that its sensitivity correlated with the infection intensity in mice. Moreover, this method had better potential utility for evaluating the treatment efficacy of PZQ in schistosome-infected mice than SEA-based ELISA.
PubMed: 37835674
DOI: 10.3390/ani13193068 -
Tropical Medicine and Infectious Disease Dec 2023Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in...
From Perpetual Wetness to Soil Chemistry: Enumerating Environmental and Physicochemical Factors Favoring Snail Presence in the Municipality of Gonzaga, Cagayan, Philippines.
Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in the Philippines, has a very focal distribution; thus, scrutinizing baseline data and parameters affecting this distribution is very crucial. In this study in Gonzaga, Cagayan, Philippines, snail habitats were surveyed, and the various factors affecting the existence of the snails were determined. Malacological surveys and the mapping of sites of perpetual wetness in five endemic and five neighboring non-endemic barangays were conducted. Environmental and physicochemical factors were also examined. Maps of both snail and non-snail sites were generated. Of the fifty sites surveyed, were found in twelve sites, and two sites yielded snails that were infected with cercariae. Factors such as silty loam soil, proximity to a snail site, water ammonia, and soil attributes (organic matter, iron, and pH) are all significantly associated with the presence of snails. In contrast, types of habitats, temperatures, and soil aggregation have no established association with the existence of snails. Mapping snail sites and determining factors favoring snail presence are vital to eliminating snails. These approaches will significantly maximize control impact and minimize wasted efforts and resources, especially in resource-limited schistosomiasis endemic areas.
PubMed: 38251207
DOI: 10.3390/tropicalmed9010009 -
PLoS Neglected Tropical Diseases Oct 2023In 1971, scientists from Mahidol University in Thailand and the Smithsonian Institution in the USA formed a research team to study a new species of Schistosoma in the...
In 1971, scientists from Mahidol University in Thailand and the Smithsonian Institution in the USA formed a research team to study a new species of Schistosoma in the Mekong River in Thailand and Laos. The studies, completed during 1971-1973, prior to the construction of any dams or restrictions to the natural flow regime of the Mekong River, provide a unique description of the natural ecological state of the river that can serve as a baseline for current research. The natural transmission of Schistosoma japonicum, Mekong Strain, was first reported on Khong Island, Laos in 1973 using sentinel mice. The first detailed description of the habitat ecology of the snail vector Neotricula aperta was done on-site in 1971 simultaneously with that research and is unique in providing the only description of the river shoreline habitat before any dams were built and any alteration of the natural flow regime was in place. Aggregating current information in a Place-Based Conceptual Model (PBCM) as an organizing template, along with current habitat models that combine ecological data with e-flows, can be developed and used as a tool to predict suitable habitats for snails. The natural flow regime of the Mekong River prior to any impoundments is described with current updates on the potential impacts of climate change and dams with flow-related snail habitat characteristics, including sediment drift and water quality. The application of the PBCM to describe and compare descriptive information on current and potential future N. aperta/S. mekongi habitat is discussed.
Topics: Humans; Animals; Mice; Schistosomiasis; Rivers; Schistosoma; Snails; Schistosoma japonicum; Ecosystem
PubMed: 37801463
DOI: 10.1371/journal.pntd.0011122 -
Journal of Biomolecular Structure &... Aug 2023Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in...
Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in the filarial nematode (AsnRS) and the parasitic flatworm (AsnRS), indicating a possible immune function. The suggestion is supported by AsnRS alleviating disease symptoms in a T-cell transfer mouse model of colitis. This immunomodulatory function is potentially related to an N-terminal extension domain present in eukaryotic AsnRS proteins but few structure/function studies have been done on this domain. Here we have determined the three-dimensional solution structure of the N-terminal extension domain of AsnRS. A protein containing the 114 N-terminal amino acids of AsnRS was recombinantly expressed with isotopic labelling to allow structure determination using 3D NMR spectroscopy, and analysis of dynamics using NMR relaxation experiments. Structural comparisons of the N-terminal extension domain of AsnRS with filarial and human homologues highlight a high degree of variability in the β-hairpin region of these eukaryotic N-AsnRS proteins, but similarities in the disorder of the C-terminal regions. Limitations in PrDOS-based intrinsically disordered region (IDR) model predictions were also evident in this comparison. Empirical structural data such as that presented in our study for N-AsnRS will enhance the prediction of sequence-homology based structure modelling and prediction of IDRs in the future.Communicated by Ramaswamy H. Sarma.
PubMed: 37572327
DOI: 10.1080/07391102.2023.2241918 -
PLoS Neglected Tropical Diseases Feb 2024Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal...
Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.
Topics: Mice; Humans; Animals; Schistosomiasis mansoni; Schistosomiasis; Schistosoma japonicum; Biomarkers; Early Diagnosis; Disease Progression
PubMed: 38381759
DOI: 10.1371/journal.pntd.0011966 -
Tropical Medicine and Infectious Disease Mar 2024In the published publication [...].
In the published publication [...].
PubMed: 38535890
DOI: 10.3390/tropicalmed9030062 -
Scientific Reports Jun 2024Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts...
Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.
Topics: Animals; Humans; Proteomics; Schistosoma; Schistosomiasis; Transcriptome; Molecular Docking Simulation; Focal Adhesion Protein-Tyrosine Kinases; Helminth Proteins; Gene Expression Profiling; Protein Kinase Inhibitors; Proteome
PubMed: 38839835
DOI: 10.1038/s41598-024-63869-0 -
Parasitology Mar 2024Schistosomiasis, a parasite infectious disease caused by , often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released...
Schistosomiasis, a parasite infectious disease caused by , often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. , the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
Topics: Humans; Mice; Animals; Schistosomiasis japonica; Ribonucleases; Endothelial Cells; Liver Cirrhosis; Schistosoma japonicum; Liver; Inflammation
PubMed: 38105713
DOI: 10.1017/S0031182023001361 -
The Journal of Biological Chemistry Jan 2024Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a...
Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPM, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPM through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPM reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPM is distinct from the TRP channel targeted by PZQ (TRPM), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPM as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ.
Topics: Animals; Humans; Anthelmintics; Benzodiazepines; Benzodiazepinones; Clonazepam; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; TRPM Cation Channels
PubMed: 38043794
DOI: 10.1016/j.jbc.2023.105528