Dataset Information

Resource fluctuations inhibit the reproduction and virulence of the human parasite Schistosoma mansoni in its snail intermediate host.

ABSTRACT: Resource availability can powerfully influence host-parasite interactions. However, we currently lack a mechanistic framework to predict how resource fluctuations alter individual infection dynamics. We address this gap with experiments manipulating resource supply and starvation for a human parasite, Schistosoma mansoni, and its snail intermediate host to test a hypothesis derived from mechanistic energy budget theory: resource fluctuations should reduce schistosome reproduction and virulence by inhibiting parasite ingestion of host biomass. Low resource supply caused hosts to remain small, reproduce less and produce fewer human-infectious cercariae. Periodic starvation also inhibited cercarial production and prevented infection-induced castration. The periodic starvation experiment also revealed substantial differences in fit between two bioenergetic model variants, which differ in their representation of host starvation. Simulations using the best-fit parameters of the winning model suggest that schistosome performance substantially declines with resource fluctuations with periods greater than 7 days. These experiments strengthen mechanistic theory, which can be readily scaled up to the population level to understand key feedbacks between resources, host population dynamics, parasitism and control interventions. Integrating resources with other environmental drivers of disease in an explicit bioenergetic framework could ultimately yield mechanistic predictions for many disease systems.

SUBMITTER: Civitello DJ

PROVIDER: S-EPMC7015343 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Resource fluctuations inhibit the reproduction and virulence of the human parasite <i>Schistosoma mansoni</i> in its snail intermediate host.

Civitello David J DJ Baker Lucy H LH Maduraiveeran Selvaganesh S Hartman Rachel B RB

Proceedings. Biological sciences 20200122 1919

Resource availability can powerfully influence host-parasite interactions. However, we currently lack a mechanistic framework to predict how resource fluctuations alter individual infection dynamics. We address this gap with experiments manipulating resource supply and starvation for a human parasite, <i>Schistosoma mansoni</i>, and its snail intermediate host to test a hypothesis derived from mechanistic energy budget theory: resource fluctuations should reduce schistosome reproduction and viru ...[more]

PMID: 31964301

Similar Datasets

Project description:The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G protein coupled receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration, these receptors control parasite reproduction and can therefore be considered as potential targets for anti-schistosome therapies.

Project description:BackgroundSnails of the genus Biomphalaria are intermediate hosts of Schistosoma mansoni, the causative agent of the human intestinal schistosomiasis. Two Biomphalaria species (Biomphalaria pfeifferi and Biomphalaria camerunensis) are involved in the transmission in Cameroon, where the disease is present nationwide. However, difficulty in the identification of both vectors impedes proper assessment of the epidemiological burden caused by each species. To overcome this issue, we designed a PCR-based molecular diagnostic tool to improve the identification of these species.MethodsWe analyzed the internal transcribed spacer 2 (ITS2) region of Biomphalaria ribosomal DNA (rDNA) using polymerase chain reaction amplification (PCR) and restriction fragment length polymorphism (RFLP).ResultsThe amplification of the ITS2 region of Biomphalaria snails resulted in a 490 bp fragment and produced two profiles for each species after digestion with the restriction enzyme Hpa II. The profile 1 (Bc-HpaII-1: 212-bp and 139-bp bands) for B. camerunensis, was common in all the sampling points; the profile 2 (Bc-HpaII-2: 212-bp and 189-bp bands), was only observed in the Lake Monoun Njindoun sampling site. Biomphalaria pfeifferi profile 1 (Bpf-HpaII-1: 211-bp and 128-bp bands) was common in most of B. pfeifferi sampling points; the profile 2 (Bpf-HpaII-2: 289-bp and 128-bp bands) was only observed in Mokolo (Far North Cameroon).The second restriction enzyme TaqαI, revealed three band profiles, Bc-TaqαI-1 (243-bp, 136-bp and 118-bp bands) and Bc-TaqαI-2 (244-bp, 136-bp and 99-bp) for B. camerunensis and Bpf-TaqαI-1 (242-bp, 135-bp and 107-bp bands) for B. pfeifferi. Sequencing analysis revealed the occurrence of six haplotypes for B. camerunensis and three haplotypes for B. pfeifferi. The level of gene flow was low and the Biomphalaria populations were not in demographic expansion according to neutrality tests (Tajima's D and Fu's Fs).ConclusionsThe PCR-RFLP technique revealed genetic diversity in Biomphalaria snails, and the combination with the morphological method could improve the identification of B. pfeifferi and B. camerunensis in Cameroon. This could help focus on the infection to evaluate the transmission risk with respect of the different species and to develop efficient and cost-effective control measures.

Project description:IntroductionThe human blood fluke parasite Schistosoma mansoni relies on diverse mechanisms to adapt to its diverse environments and hosts. Epigenetic mechanisms play a central role in gene expression regulation, culminating in such adaptations. Protein arginine methyltransferases (PRMTs) promote posttranslational modifications, modulating the function of histones and non-histone targets. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is one of the S. mansoni proteins with the PRMT core domain.MethodsWe carried out in silico analyses to verify the expression of SmPRMTs in public datasets from different infection stages, single-sex versus mixed-worms, and cell types. The SmCARM1 function was evaluated by RNA interference. Gene expression levels were assessed, and phenotypic alterations were analyzed in vitro, in vivo, and ex vivo.ResultsThe scRNAseq data showed that SmPRMTs expression is not enriched in any cell cluster in adult worms or schistosomula, except for Smcarm1 expression which is enriched in clusters of ambiguous cells and Smprmt1 in NDF+ neurons and stem/germinal cells from schistosomula. Smprmt1 is also enriched in S1 and late female germ cells from adult worms. After dsRNA exposure in vitro, we observed a Smcarm1 knockdown in schistosomula and adult worms, 83 and 69%, respectively. Smcarm1-knockdown resulted in reduced oviposition and no significant changes in the schistosomula or adult worm phenotypes. In vivo analysis after murine infection with Smcarm1 knocked-down schistosomula, showed no significant change in the number of worms recovered from mice, however, a significant reduction in the number of eggs recovered was detected. The ex vivo worms presented a significant decrease in the ovary area with a lower degree of cell differentiation, vitelline glands cell disorganization, and a decrease in the testicular lobe area. The worm tegument presented a lower number of tubercles, and the ventral sucker of the parasites presented a damaged tegument and points of detachment from the parasite body.DiscussionThis work brings the first functional characterization of SmCARM1 shedding light on its roles in S. mansoni biology and its potential as a drug target. Additional studies are necessary to investigate whether the reported effects of Smcarm1 knockdown are a consequence of the SmCARM1-mediated methylation of histone tails involved in DNA packaging or other non-histone proteins.

Project description:BackgroundBiomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi.Methodology/principal findingsBased largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago.Conclusions/significanceThe genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.

Dataset Information

Resource fluctuations inhibit the reproduction and virulence of the human parasite Schistosoma mansoni in its snail intermediate host.

Publications

Resource fluctuations inhibit the reproduction and virulence of the human parasite <i>Schistosoma mansoni</i> in its snail intermediate host.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets