The cell biology of schistosomes: a window on the evolution of the early metazoa

Wilson, R. A.

doi:10.1007/s00709-011-0326-x

Cited by 16 publications

(20 citation statements)

References 103 publications

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“…The integrity and function of the surface tegumental membrane are critical to the survival and proliferation of Schistosoma . The tegument, a syncytium covered by two lipid bilayers that is a unique structure to all trematodes [46] – [49] . In fact the two lipid bilayer structure pertains only to trematodes that live within blood vessels [50] , plays vital roles like evasion of the immune system, acquisition of nutrients, excretion of catabolic products, targeted drug absorption and other physiological processes [47] , [49] , [51] – [54] .…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

et al. 2014

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BackgroundSchistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites.Methodology/Principal FindingsWe found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis.Conclusions/SignificanceOur data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni-infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

et al. 2014

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“…SmKK7, for example, was first described as a secreted putative potassium channel blocker present in secretions from mechanically transformed cercariae [26]. The protein was later revealed to be present in the ciliated sensory endings (reviewed in [30]) rather than in acetabular glands. Thus, another important contribution of our work was the establishment of the precise site of gene expression for proteins that have been previously detected by high throughput proteomic studies of cercarial secretions.…”

Section: Discussionmentioning

confidence: 99%

Stage and tissue expression patterns of Schistosoma mansoni venom allergen-like proteins SmVAL 4, 13, 16 and 24

et al. 2017

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Background Schistosoma mansoni venom allergen-like protein (SmVAL) is a gene family composed of 29 members divided into group 1 encoding proteins potentially secreted, and group 2 encoding intracellular components. Some members were found to be upregulated in the transition of germ ball - cercariae - day 3 schistosomula, suggesting that group 1 SmVAL proteins are associated with the invasion of the human host, although their functions are not completely established. Recently, we have described the localization of SmVAL7 (group 1) and SmVAL6 (group 2) transcripts in the oesophageal gland and in the oral and ventral suckers of adult parasites, respectively. The expression patterns of the two genes suggest that SmVAL7 protein plays a role in the blood-feeding process while SmVAL6 is associated with the parasite attachment and movement in the vasculature. In this way, searching for additional secreted SmVAL proteins that could be involved in key processes from skin penetration to the beginning of blood-feeding, we investigated the tissue localization of SmVAL4, 13, 16 and 24 by whole-mount in situ hybridization (WISH).ResultsWe report here the localization of group 1 SmVAL4 and 24 transcripts in the pre-acetabular glands of developing germ balls. Time course experiments of in vitro cultured schistosomula after cercariae transformation demonstrated that SmVAL4 protein is secreted during the first 3 h of in vitro culture, correlating with the emptying of acetabular glands as documented by confocal microscopy. In addition, the localization of SmVAL13 transcripts in adult male anterior oesophageal gland suggests that the respective protein may be involved in the first steps of the blood-feeding process. SmVAL16 was localized close to the neural ganglia and requires further investigation.ConclusionsOur findings demonstrate that SmVAL proteins have localizations that place them in strategic positions to be considered as potential vaccine candidates as some members are exposed to interaction with the immune system and may participate in key processes of mammalian invasion and parasitism establishment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2144-2) contains supplementary material, which is available to authorized users.

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“…The tegument is an essential structure for the survival and maintenance of Schistosoma worms because it plays a vital role in evading the host’s immune system, acquiring nutrients, excreting catabolic products, and targeting drug absorption, among other physiological processes [52]. …”

Section: Discussionmentioning

confidence: 99%

Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms

et al. 2016

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Inducing apoptosis is an interesting therapeutic approach to develop drugs that act against helminthic parasites. Researchers have investigated how curcumin (CUR), a biologically active compound extracted from rhizomes of Curcuma longa, affects Schistosoma mansoni and several cancer cell lines. This study evaluates how CUR influences the induction of apoptosis and oxidative stress in couples of adult S. mansoni worms. CUR decreased the viability of adult worms and killed them. The tegument of the parasite suffered morphological changes, the mitochondria underwent alterations, and chromatin condensed. Different apoptotic parameters were determined in an attempt to understand how CUR affected adult S. mansoni worms. CUR induced DNA damage and fragmentation and increased the expression of SmCASP3/7 transcripts and the activity of Caspase 3 in female and male worms. However, CUR did not intensify the activity of Caspase 8 in female or male worms. Evaluation of the superoxide anion and different antioxidant enzymes helped to explore the mechanism of parasite death further. The level of superoxide anion and the activity of Superoxide Dismutase (SOD) increased, whereas the activity of Glutathione-S-Transferase (GST), Glutathione reductase (GR), and Glutathione peroxidase (GPX) decreased, which culminated in the oxidation of proteins in adult female and male worms incubated with CUR. In conclusion, CUR generated oxidative stress followed by apoptotic-like-events in both adult female and male S. mansoni worms, ultimately killing them.

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The cell biology of schistosomes: a window on the evolution of the early metazoa

Cited by 16 publications

References 103 publications

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

Stage and tissue expression patterns of Schistosoma mansoni venom allergen-like proteins SmVAL 4, 13, 16 and 24

Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms

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