Aerobic to anaerobic transition in the carbohydrate metabolism of Schistosoma mansoni cercariae during transformation in vitro

Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 409-415 ◽  
Author(s):  
B. E. P. Van Oordt ◽  
A. G. M. Tielens ◽  
S. G. Van Den Bergh
Keyword(s):  
Carbon Dioxide ◽  
Electron Transfer ◽  
Schistosoma Mansoni ◽  
Krebs Cycle ◽  
Salt Medium ◽  
Metabolic Transition ◽  
Biological Transformation ◽  
Lactate And Pyruvate ◽  
Aerobic Energy Metabolism

SUMMARYSchistosoma mansoni cercariae in water were shown to possess a largely aerobic energy metabolism, the Krebs cycle being the main terminal of carbohydrate breakdown. A metabolic transition towards a more anaerobic breakdown of carbo-hydrate could be achieved by incubation conditions which also stimulated biological transformation. Incubation of cercariae in a simple salt medium containing 5 mM glucose induced such a metabolic transition: beside carbon dioxide large amounts of lactate and pyruvate were excreted. The results indicate that the production of pyruvate was coupled to electron transfer in the respiratory chain. Some aspects of this unusual pyruvate production are discussed. The observed change in the end-product pattern of carbohydrate breakdown is very rapid: most of the switch occurred within 2 h. Our results show that the metabolic transition was triggered by the biological transformation itself, or by the same event that induces the biological transformation. The metabolic and the biological changes proceeded synchronously.

The transition from an aerobic to an anaerobic energy metabolism in transforming Schistosoma mansoni cercariae occurs exclusively in the head

Parasitology ◽  
1991 ◽  
Vol 102 (2) ◽  
pp. 259-265 ◽  
Author(s):  
A. M. C. Horemans ◽  
A. G. M. Tielens ◽  
S. G. Van Den Bergh
Keyword(s):  
Carbon Dioxide ◽  
Energy Metabolism ◽  
Schistosoma Mansoni ◽  
Salt Medium ◽  
Metabolic Switch ◽  
Anaerobic Energy ◽  
Metabolic Transition ◽  
Rapid Transition ◽  
Lactate And Pyruvate ◽  
Aerobic Energy Metabolism

SUMMARYIt has been shown that in intact cercariae of Schistosoma mansoni in water, both head and tail had an identical, aerobic energy metabolism. As long as the environment was water, glucose was mainly degraded to carbon dioxide by both head and tail whether or not these two were still connected to each other. Transfer of intact cercariae into a simple salt medium supplemented with glucose resulted in a very rapid transition towards a more anaerobic energy metabolism: the production of lactate and pyruvate increased, whereas the production of carbon dioxide remained more or less constant. A concomitant rise in temperature to 37°C was not essential for this biochemical transition, but made it more pronounced. Experiments on isolated cercarial bodies and tails in a transforming medium demonstrated that the tails oxidized glucose to carbon dioxide, whereas bodies produced mainly pyruvate and lactate. The results showed that the metabolic transition towards a more anaerobic energy metabolism occurred only in the head and not in the tail of the cercariae. Loss of the tail was shown not to be a pre-requisite for this transition, nor did it by itself trigger a metabolic switch in the resulting cercarial body.

Synthesis and degradation of glycogen by Schistosoma mansoni worms in vitro

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 67-73 ◽  
Author(s):  
A. G. M. Tielens ◽  
C. Celik ◽  
J. M. Van Den Heuvel ◽  
R. H. Elfring ◽  
S. G. Van Den Bergh
Keyword(s):  
Schistosoma Mansoni ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Krebs Cycle ◽  
Glycogen Metabolism ◽  
Mammalian Host ◽  
Initial Reduction ◽  
Glycogen Stores ◽  
Synthesis And Degradation

SummaryThe glycogen stores of adult Schistosoma mansoni worms could be labelled by incubation of the worms, after an initial reduction of their glycogen content, in the presence of [6-14C]glucose. Subsequent breakdown of the labelled glycogen by the parasite revealed that glycogen was degraded to lactate and carbon dioxide. The degradation of glycogen, as compared to that of glucose, resulted in slightly different ratios of these two end-products. This indicates that glycogen breakdown did not replace glucose breakdown to the same extent in all cells and that Krebs-cycle activity was not uniformly distributed throughout the cells of this parasite. Both fructose and mannose could replace glucose as an energy source and the rate of glycogen synthesis from either of these two carbohydrates was higher than from glucose. No indications for glyconeogenesis from C3-units were found. Glycogen metabolism of S. mansoni was not influenced by hormones of the mammalian host. It is regulated by the external glucose concentration and by the level of the endogenous glycogen stores. Studies on paired and unpaired worms showed that no interaction between male and female was necessary for the synthesis of glycogen by female worms.

In vitro schistosomicidal activity of Usnea steineri extract and its major constituent (+)-usnic acid against Schistosoma mansoni

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
AIO Salloum ◽  
R Lucarini ◽  
MG Tozatti ◽  
J Medeiros ◽  
MLA Silva ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Usnic Acid ◽  
Major Constituent

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals Novel Transcriptional Regulons for Autotrophic Cycle Genes in Crenarchaeota

2015 ◽  
Vol 197 (14) ◽  
pp. 2383-2391 ◽  
Author(s):  
Semen A. Leyn ◽  
Irina A. Rodionova ◽  
Xiaoqing Li ◽  
Dmitry A. Rodionov
Keyword(s):  
Carbon Dioxide ◽  
Transcriptional Regulation ◽  
Comparative Genomics ◽  
Dna Binding ◽  
Transcriptional Control ◽  
Binding Assays ◽  
Promoter Regions ◽  
Content Type ◽  
Genome Context

ABSTRACTAutotrophic microorganisms are able to utilize carbon dioxide as their only carbon source, or, alternatively, many of them can grow heterotrophically on organics. Different variants of autotrophic pathways have been identified in various lineages of the phylumCrenarchaeota. Aerobic members of the orderSulfolobalesutilize the hydroxypropionate-hydroxybutyrate cycle (HHC) to fix inorganic carbon, whereas anaerobicThermoprotealesuse the dicarboxylate-hydroxybutyrate cycle (DHC). Knowledge of transcriptional regulation of autotrophic pathways inArchaeais limited. We applied a comparative genomics approach to predict novel autotrophic regulons in theCrenarchaeota. We report identification of two novel DNA motifs associated with the autotrophic pathway genes in theSulfolobales(HHC box) andThermoproteales(DHC box). Based on genome context evidence, the HHC box regulon was attributed to a novel transcription factor from the TrmB family named HhcR. Orthologs of HhcR are present in allSulfolobalesgenomes but were not found in other lineages. A predicted HHC box regulatory motif was confirmed byin vitrobinding assays with the recombinant HhcR protein fromMetallosphaera yellowstonensis. For the DHC box regulon, we assigned a different potential regulator, named DhcR, which is restricted to the orderThermoproteales. DhcR inThermoproteus neutrophilus(Tneu_0751) was previously identified as a DNA-binding protein with high affinity for the promoter regions of two autotrophic operons. The global HhcR and DhcR regulons reconstructed by comparative genomics were reconciled with available omics data inMetallosphaeraandThermoproteusspp. The identified regulons constitute two novel mechanisms for transcriptional control of autotrophic pathways in theCrenarchaeota.IMPORTANCELittle is known about transcriptional regulation of carbon dioxide fixation pathways inArchaea. We previously applied the comparative genomics approach for reconstruction of DtxR family regulons in diverse lineages ofArchaea. Here, we utilize similar computational approaches to identify novel regulatory motifs for genes that are autotrophically induced in microorganisms from two lineages ofCrenarchaeotaand to reconstruct the respective regulons. The predicted novel regulons in archaeal genomes control the majority of autotrophic pathway genes and also other carbon and energy metabolism genes. The HhcR regulon was experimentally validated by DNA-binding assays inMetallosphaeraspp. Novel regulons described for the first time in this work provide a basis for understanding the mechanisms of transcriptional regulation of autotrophic pathways inArchaea.

scholarly journals MECHANISM OF FIXATION OF CARBON DIOXIDE IN THE KREBS CYCLE

1941 ◽  
Vol 139 (1) ◽  
pp. 483-484
Author(s):  
H.G. Wood ◽  
C.H. Werkman ◽  
Allan Hemingway ◽  
A.O. Nier
Keyword(s):  
Carbon Dioxide ◽  
Krebs Cycle ◽  
Fixation Of Carbon Dioxide

scholarly journals Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

2021 ◽  
Vol 14 (7) ◽  
pp. 686
Author(s):  
Raquel Porto ◽  
Ana C. Mengarda ◽  
Rayssa A. Cajas ◽  
Maria C. Salvadori ◽  
Fernanda S. Teixeira ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Screening Strategy ◽  
Early Infection ◽  
Global Public Health ◽  
Parasitic Worm ◽  
Electron Microscopy Analysis ◽  
Health Significance ◽  
Microscopy Analysis

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

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