The Experts below are selected from a list of 6423 Experts worldwide ranked by ideXlab platform
Maggie Fisher - One of the best experts on this subject based on the ideXlab platform.
-
an abies procera derived tetracyclic triterpene containing a steroid like nucleus core and a lactone side chain attenuates in vitro survival of both fasciola hepatica and schistosoma mansoni
International Journal for Parasitology-Drugs and Drug Resistance, 2018Co-Authors: Helen L. Whiteland, Anand Chakroborty, Alessandra Crusco, Alan Cookson, Jackie Hollinshead, Caroline A. Fenn, Barbara Bartholomew, Peter A. Holdsworth, Josephine Fordethomas, Maggie FisherAbstract:Abstract Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature Flukes, 2 for mature Flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature Flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood Flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis.
-
An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni
Elsevier, 2018Co-Authors: Helen L. Whiteland, Anand Chakroborty, Josephine E. Forde-thomas, Alessandra Crusco, Alan Cookson, Jackie Hollinshead, Caroline A. Fenn, Barbara Bartholomew, Peter A. Holdsworth, Maggie FisherAbstract:Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature Flukes, 2 for mature Flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature Flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood Flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis. Keywords: Abies procera, Abies grandis, Triterpenoid, Anthelmintic drug discovery, Neglected tropical diseases, Fasciola hepatica, Schistosoma manson
Helen L. Whiteland - One of the best experts on this subject based on the ideXlab platform.
-
an abies procera derived tetracyclic triterpene containing a steroid like nucleus core and a lactone side chain attenuates in vitro survival of both fasciola hepatica and schistosoma mansoni
International Journal for Parasitology-Drugs and Drug Resistance, 2018Co-Authors: Helen L. Whiteland, Anand Chakroborty, Alessandra Crusco, Alan Cookson, Jackie Hollinshead, Caroline A. Fenn, Barbara Bartholomew, Peter A. Holdsworth, Josephine Fordethomas, Maggie FisherAbstract:Abstract Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature Flukes, 2 for mature Flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature Flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood Flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis.
-
An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni
Elsevier, 2018Co-Authors: Helen L. Whiteland, Anand Chakroborty, Josephine E. Forde-thomas, Alessandra Crusco, Alan Cookson, Jackie Hollinshead, Caroline A. Fenn, Barbara Bartholomew, Peter A. Holdsworth, Maggie FisherAbstract:Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature Flukes, 2 for mature Flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature Flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood Flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis. Keywords: Abies procera, Abies grandis, Triterpenoid, Anthelmintic drug discovery, Neglected tropical diseases, Fasciola hepatica, Schistosoma manson
Banchob Sripa - One of the best experts on this subject based on the ideXlab platform.
-
a comparative study of helicobacter pylori infection in hamsters experimentally infected with liver Flukes opisthorchis felineus opisthorchis viverrini or clonorchis sinensis
Scientific Reports, 2021Co-Authors: Mariya Y Pakharukova, Banchob Sripa, Oxana Zaparina, Sungjong Hong, Viatcheslav A MordvinovAbstract:Helicobacter pylori causes a wide range of human diseases including cancer. Carcinogenic foodborne trematodes Opisthorchis viverrini, Clonorchis sinensis, and O. felineus might promote transmission and spread of H. pylori infection in the definitive mammalian host, which in turn might contribute to the liver fluke-associated malignancy. Our objectives were to find out whether liver Flukes O. felineus, O. viverrini, and C. sinensis are carriers of Helicobacter pylori and to determine whether H. pylori is present in feces, bile, and stomach samples from the experimentally infected hamsters. We found that liver Flukes are not reservoirs of H. pylori. Nevertheless, the prevalence of H. pylori and the H. pylori ureA gene copy number were significantly elevated after the infection. Overall, although the liver Flukes O. felineus, C. sinensis, and O. viverrini are not reservoirs of H. pylori, the infection with the liver Flukes significantly modifies the biliary and gut microbiota by increasing H. pylori abundance. This may be a feature of any liver fluke pathogenesis that have not previously been taken into account. Our findings appear to be novel in terms of comparative assessment of the host microbiota and Helicobacter abundance during epidemiologically important liver fluke infections.
-
programmed mutation of liver fluke granulin using crispr cas9 attenuates virulence of infection induced hepatobiliary morbidity
bioRxiv, 2018Co-Authors: Patpicha Arunsan, Michael J. Smout, Christina J Cochran, Shannon E Karinshak, Banchob Sripa, Victoria H. Mann, Neil D. Young, Wannaporn Ittiprasert, Sujittra Chaiyadet, Javier SotilloAbstract:Infections with several flatworm parasites represent group 1 biological carcinogens, i.e. definite causes of cancer. Infection with the food-borne liver fluke Opisthorchis viverrini causes cholangiocarcinoma (CCA). Whereas the causative agent for most cancers, including CCA in the West, remains obscure, the principal risk factor for CCA in Thailand is opisthorchiasis. We exploited this established link to explore the role of the secreted parasite growth factor termed liver fluke granulin (Ov-GRN-1) in pre-malignant lesions of the biliary tract. We targeted the Ov-grn-1 gene for programmed knockout and investigated gene-edited parasites in vitro and in experimentally infected hamsters. Both adult and juvenile stages of the liver fluke were transfected with a plasmid encoding a guide RNA sequence specific for exon 1 of Ov-grn-1 and the Cas9 nuclease. Deep sequencing of amplicon libraries from genomic DNA from gene-edited parasites exhibited programmed, Cas9-catalyzed mutations within the Ov-grn-1 locus, and tandem analyses by RT-PCR and western blot revealed rapid depletion of Ov-grn-1 transcripts and protein. Newly excysted juvenile Flukes that had undergone editing of Ov-grn-1 colonized the biliary tract, grew and developed over a period of 60 days, were active and motile, and induced a clinically relevant pathophysiological tissue phenotype of attenuated biliary hyperplasia and fibrosis in comparison to infection with wild type Flukes. This is the first report of gene knock-out using CRISPR/Cas9 in a parasitic flatworm, demonstrating the activity and utility of the process for functional genomics in these pathogens. The striking clinical phenotype highlights the role in virulence that liver fluke growth factors play in biliary tract morbidity during chronic opisthorchiasis.
-
suppression of mrnas encoding cd63 family tetraspanins from the carcinogenic liver fluke opisthorchis viverrini results in distinct tegument phenotypes
Scientific Reports, 2017Co-Authors: Sujittra Chaiyadet, Michael J. Smout, Javier Sotillo, Banchob Sripa, Paul J Brindley, Supawadee Piratae, Watchara Krueajampa, Wiphawi Hipkaeo, Yada Plosan, Alex LoukasAbstract:The liver fluke Opisthorchis viverrini infects 10 million people in Southeast Asia and causes cholangiocarcinoma (CCA). Fluke secreted and tegumental proteins contribute to the generation of a tumorigenic environment and are targets for drug and vaccine-based control measures. Herein, we identified two tetraspanins belonging to the CD63 family (Ov-TSP-2 and Ov-TSP-3) that are abundantly expressed in the tegument proteome of O. viverrini. Ov-tsp-2 and tsp-3 transcripts were detected in all developmental stages of O. viverrini. Protein fragments corresponding to the large extracellular loop (LEL) of each TSP were produced in recombinant form and antibodies were raised in rabbits. Ov-TSP-2 and TSP-3 were detected in whole worm extracts and excretory/secretory products of O. viverrini and reacted with sera from infected hamsters and humans. Antibodies confirmed localization of Ov-TSP-2 and TSP-3 to the adult fluke tegument. Using RNA interference, Ov-tsp-2 and tsp-3 mRNA expression was significantly suppressed for up to 21 days in vitro. Ultrastructural observation of tsp-2 and tsp-3 dsRNA-treated Flukes resulted in phenotypes with increased tegument thickness, increased vacuolation (tsp-2) and reduced electron density (tsp-3). These studies confirm the importance of CD63 family tegument tetraspanins in parasitic Flukes and support efforts to target these proteins for vaccine development.
-
unusual thiol based redox metabolism of parasitic Flukes
Parasitology International, 2017Co-Authors: Timir Tripathi, Sutas Suttiprapa, Banchob SripaAbstract:Parasitic Flukes are exposed to free radicals and, to a greater extent, reactive oxygen species (ROS) during their life cycle. Despite being relentlessly exposed to ROS released by activated immune cells, these parasites can survive for many years in the host. Cellular thiol-based redox metabolism plays a crucial role in parasite survival within their hosts. Evidence shows that oxidative stress and redox homeostasis maintenance are important clinical and pathobiochemical as well as effective therapeutic principles in various diseases. The characterization of redox and antioxidant enzymes is likely to yield good target candidates for novel drugs and vaccines. The absence of active catalase in fluke parasites offers great potential for the development of chemotherapeutic agents that act by perturbing the redox equilibrium of the cell. One of the redox-sensitive enzymes, thioredoxin glutathione reductase (TGR), has been accepted as a drug target against blood fluke infections, and related clinical trials are in progress. TGR is the sole enzyme responsible for Trx and GSH reduction in parasitic Flukes. The availability of helminth genomes has accelerated the research on redox metabolism of Flukes; however, significant achievements have yet to be attained. The present review summarizes current knowledge on the redox and antioxidant system of the parasitic Flukes.
-
The role of evolutionary biology in research and control of liver Flukes in Southeast Asia.
Infection genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2016Co-Authors: Pierre Echaubard, Banchob Sripa, Frank F. Mallory, Bruce A. WilcoxAbstract:Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology-based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework.
Paul J Brindley - One of the best experts on this subject based on the ideXlab platform.
-
suppression of mrnas encoding cd63 family tetraspanins from the carcinogenic liver fluke opisthorchis viverrini results in distinct tegument phenotypes
Scientific Reports, 2017Co-Authors: Sujittra Chaiyadet, Michael J. Smout, Javier Sotillo, Banchob Sripa, Paul J Brindley, Supawadee Piratae, Watchara Krueajampa, Wiphawi Hipkaeo, Yada Plosan, Alex LoukasAbstract:The liver fluke Opisthorchis viverrini infects 10 million people in Southeast Asia and causes cholangiocarcinoma (CCA). Fluke secreted and tegumental proteins contribute to the generation of a tumorigenic environment and are targets for drug and vaccine-based control measures. Herein, we identified two tetraspanins belonging to the CD63 family (Ov-TSP-2 and Ov-TSP-3) that are abundantly expressed in the tegument proteome of O. viverrini. Ov-tsp-2 and tsp-3 transcripts were detected in all developmental stages of O. viverrini. Protein fragments corresponding to the large extracellular loop (LEL) of each TSP were produced in recombinant form and antibodies were raised in rabbits. Ov-TSP-2 and TSP-3 were detected in whole worm extracts and excretory/secretory products of O. viverrini and reacted with sera from infected hamsters and humans. Antibodies confirmed localization of Ov-TSP-2 and TSP-3 to the adult fluke tegument. Using RNA interference, Ov-tsp-2 and tsp-3 mRNA expression was significantly suppressed for up to 21 days in vitro. Ultrastructural observation of tsp-2 and tsp-3 dsRNA-treated Flukes resulted in phenotypes with increased tegument thickness, increased vacuolation (tsp-2) and reduced electron density (tsp-3). These studies confirm the importance of CD63 family tegument tetraspanins in parasitic Flukes and support efforts to target these proteins for vaccine development.
-
suppression of ov grn 1 encoding granulin of opisthorchis viverrini inhibits proliferation of biliary epithelial cells
Experimental Parasitology, 2015Co-Authors: Atiroch Papatpremsiri, Michael J. Smout, Banchob Sripa, Alex Loukas, Paul J Brindley, Thewarach LahaAbstract:Multistep processes likely underlie cholangiocarcinogenesis induced by chronic infection with the fish-borne liver fluke, Opisthorchis viverrini. One process appears to be cellular proliferation of the host bile duct epithelia driven by excretory–secretory (ES) products of this pathogen. Specifically, the secreted growth factor Ov-GRN-1, a liver fluke granulin, is a prominent component of ES and a known driver of hyper-proliferation of cultured human and mouse cells in vitro. We show potent hyper-proliferation of human cholangiocytes induced by low nanomolar levels of recombinant Ov-GRN-1 and similar growth produced by low microgram concentrations of ES products and soluble lysates of the adult worm. To further explore the influence of Ov-GRN-1 on the Flukes and the host cells, expression of Ov-grn-1 was repressed using RNA interference. Expression of Ov-grn-1 was suppressed by 95% by day 3 and by ~100% by day 7. Co-culture of Ov-grn-1 suppressed Flukes with human cholangiocyte (H-69) or human cholangiocarcinoma (KKU-M214) cell lines retarded cell hyper-proliferation by 25% and 92%, respectively. Intriguingly, Flukes in which expression of Ov-grn-1 was repressed were less viable in culture, suggesting that Ov-GRN-1 is an essential growth factor for survival of the adult stage of O. viverrini, at least in vitro. To summarize, specific knock down of Ov-grn-1 reduced in vitro survival and capacity of ES products to drive host cell proliferation. These findings may help to contribute to a deeper understanding of liver fluke induced cholangiocarcinogenesis.
-
infection with the carcinogenic liver fluke opisthorchis viverrini modifies intestinal and biliary microbiome
The FASEB Journal, 2013Co-Authors: Jordan L Plieskatt, Banchob Sripa, Raksawan Deenonpoe, Jason Mulvenna, Lutz Krause, Jeffrey M Bethony, Paul J BrindleyAbstract:Opisthorchis viverrini is a fish-borne trem- atode endemic in East Asia. Following ingestion, the Flukes locate to the biliary treewhere chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whole O. viverrini were examined in this model of fluke-induced CCA. Micro- bial communities were characterized by high-through- put sequencing of variable regions 7-9 of prokaryotic 16S ribosomal DNA. Of 1 million sequences, 536,009 with useable reads were assignable to 29,776 opera- tional taxonomy units (OTUs) and, in turn, to 20 phyla and 273 genera of Bacteria or Archaea. Microbial community analyses revealed that fluke infection per- turbed the gastrointestinal tract microbiome, increasing Lachnospiraceae, Ruminococcaceae, and Lactobacil- laceae, while decreasing Porphyromonadaceae, Erysip- elotrichaceae, and Eubacteriaceae (P<0.05). More than 60 OTUs were detected in the biliary system, which confirmed bacteriobilia and a noteworthy community of microbes associated with the parasites. The fluke- associated microorganisms included potential patho- gens from the Enterobacteriaceae and Listeriaceae and others, including Cyanobacteria and Deinococci, usu- ally found in external environments. Given that opis- thorchiasis is distinguished from other helminth infec- tions by a robust inflammatory phenotype with conspicuously elevated IL-6, and that inflammation of the biliary system leads to periductal fibrosis, which is a precursor of CCA, the Flukes and their microbiota may together drive this distinctive immune response.— Plieskatt, J. L., Raksawan, D., Mulvenna, J. P., Krause, L., Sripa, B., Bethony, J. M., Brindley, P. J. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. FASEB J. 27, 000-000 (2013). www.fasebj.org
-
molecular characterization of a tetraspanin from the human liver fluke opisthorchis viverrini
PLOS Neglected Tropical Diseases, 2012Co-Authors: Supawadee Piratae, Banchob Sripa, Alex Loukas, Paul J Brindley, Smarn Tesana, Malcolm K Jones, Erica Lovas, Veerachai Eursitthichai, Sirikanda Thanasuwan, Thewarach LahaAbstract:Background The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood Flukes where they are essential for tegument formation, are directly exposed to the immune system, and are major targets for a schistosomiasis vaccine. We propose that similar molecules in the surface membranes of O. viverrini are integral to tegument biogenesis and will be efficacious vaccine antigens. Methodology/Principal Findings The cDNA sequence encoding O. viverrini tetraspanin-1 (Ov-TSP-1) was identified and cloned. The Ov-tsp-1gene was isolated from a cDNA library. Ov-tsp-1 mRNA was expressed most highly in metacercariae and eggs, and to a lesser extent in juvenile and adult worms. Immunolocalization with adult Flukes confirmed that Ov-TSP-1 was expressed in the tegument and eggs in utero. Western blot analysis of rOv-TSP-1 probed with sera from O. viverrini-infected humans and hamsters indicated that both hosts raise antibody responses against the native TSP. Using RNA interference we silenced the expression level of Ov-tsp-1 mRNA in adult Flukes by up to 72% by 10 days after delivery of dsRNA. Ultrastructural morphology of adult worms treated with Ov-tsp-1 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Conclusions/Significance This is the first report of a tetraspanin from the tegument of a liver fluke. Our data imply that tetraspanins play important structural roles in the development of the tegument in the adult fluke. Potential uses of O. viverrini tetraspanins as novel interventions are discussed.
M Daintith - One of the best experts on this subject based on the ideXlab platform.
-
pathological findings in southern bluefin tuna thunnus maccoyii castelnau infected with cardicola forsteri cribb daintith munday 2000 digenea sanguinicolidae a blood fluke
Journal of Fish Diseases, 2001Co-Authors: S E Colquitt, B L Munday, M DaintithAbstract:Gills, heart ventricles and a limited number of other organs were collected from wild and captive southern bluefin tuna, and examined histologically for eggs of Cardicola forsteri. A limited number of entire hearts from farmed tuna were also examined, some of which yielded adult Flukes within the ventricles. No adult Flukes or their eggs were found in wild tuna. In infected farmed fish, fluke eggs impacted in the afferent filamentary blood vessels where they provoked a marked, but variable, inflammatory response, resulting in nodular gill lesions. No eggs were found on the efferent side of the gill vasculature, or in the compacta of the ventricle, which is supplied with blood from coronary vessels. The infection does not appear to cause mortality in farmed tuna.
