Transcriptional profiling of the oesophageal gland region of male worms of Schistosoma mansoni

Nawaratna, Sujeevi; Gobert, Geoffrey N.; Willis, Charlene; Chuah, Candy; McManus, Donald P.; Jones, Malcolm K.

doi:10.1016/j.molbiopara.2014.08.002

Cited by 19 publications

(17 citation statements)

References 31 publications

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“…The SmVAL13 gene, was first depicted as an upregulated gene in female worms by qRT-PCR [16], and then subsequently identified in the anterior region of adult male worms by microarrays [40, 41], and more recently in day 3 schistosomula [17]. Herein, we provide definitive evidence that this gene is actually expressed in the anterior oesophagus of adult male worms; we could not detect SmVAL13 expression in adult female worms by WISH.…”

Section: Discussionmentioning

confidence: 61%

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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Section: Discussionmentioning

confidence: 61%

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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“…That SmLSD1 controls the expression of genes of the digestive system of female or male worms was supported by the fact that a number of genes encoding enzymes or proteins of the digestive tract of the parasite [65] had modified expression in treated parasites (Tables S9-S11, shaded in green and with *). In this regard, it is noteworthy that blood digestion seemed to be severely compromised in females (see Supplementary Video S4).…”

Section: Discussionmentioning

confidence: 95%

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Carneiro

Silva

Amaral

et al. 2019

Preprint

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Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ), and due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935. We synthesized a novel and potent LSD1 inhibitor, MC3935, which was used to treat schistosomula or adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors.Author SummarySchistosomiasis mansoni is a chronic and debilitating tropical disease caused by the helminth Schistosoma mansoni. The control and treatment of the disease rely almost exclusively on praziquantel (PZQ). Thus, there is an urgent need to search for promising protein targets to develop new drugs. Drugs that inhibit enzymes that modify the chromatin structure have been developed for a number of diseases. We and others have shown that S. mansoni epigenetic enzymes are also potential therapeutic targets. Here we evaluated the potential of the S. mansoni histone demethylase LSD1 (SmLSD1) as a drug target. We reported the synthesis of a novel and potent LSD1 inhibitor, MC3935, and show that it selectively inhibited the enzymatic activity of SmLSD1. Treatment of juvenile or adult worms with MC3935 caused severe damage to the tegument of the parasites and compromised egg production. Importantly, MC3935 proved to be highly toxic to S. mansoni, culminating in the death of juvenile or adult worms within 96 h. Transcriptomic analysis of MC3935-treated parasites revealed changes in the gene expression of hundreds of genes involved in key biological processes. Importantly, SmLSD1 contains unique sequences within its polypeptide chain that could be explored to develop a S. mansoni selective drug.

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“…Recent studies employed this method in genome sequencing of Plasmodium relictum , where it was used to dissect the parasite from infected erythrocytes while excluding the host nucleus [16]. It has also been recently applied in a transcriptomic analysis of Plasmodium cynomolgi for dissection of hypnozoites from hepatocytes [17], in molecular analysis of Henneguya adiposa from the fins of catfish [18], and in investigation of ferritin gene expression in vitelline cells and tissue-specific gene profiling (gastrodermis, vitelline, and ovary tissue) of Schistosoma japonicum [19,20] and Schistosoma mansoni [21,22]. In a study focused on changes in protein composition in intermediate snail host, infected or uninfected by S. mansoni , the method was used to dissect hemocytes and sporocysts [23].…”

Section: Introductionmentioning

confidence: 99%

Laser capture microdissection in combination with mass spectrometry: Approach to characterization of tissue-specific proteomes ofEudiplozoon nipponicum(Monogenea, Polyopisthocotylea)

Roudnický

Potěšil²,

Zdráhal³

et al. 2020

Preprint

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23Eudiplozoon nipponicum (Goto, 1891) is a hematophagous monogenean ectoparasite 24 which inhabits the gills of the common carp (Cyprinus carpio). Heavy infestation can lead to 25 anemia and in conjunction with secondary bacterial infections cause poor health and eventual 26 death of the host. 27 This study is based on an innovative approach to protein localization which has never 28 been used in parasitology before. Using laser capture microdissection, we dissected particular 29 areas of the parasite body without contaminating the samples by surrounding tissue, and in 30 combination with analysis by mass spectrometry obtained tissue-specific proteomes of 31 tegument, intestine, and parenchyma of our model organism, E. nipponicum. We successfully 32 verified the presence of certain functional proteins (e.g. cathepsin L) in tissues where their 33 presence was expected (intestine) and confirmed that there were no traces of these proteins in 34 other tissues (tegument and parenchyma). Additionally, we identified a total of 2,059 proteins, 35 including 72 peptidases and 33 peptidase inhibitors. As expected, the greatest variety was found 36 in the intestine and the lowest variety in the parenchyma. 37Our results are significant on two levels. Firstly, we demonstrated how one can localize 38 all proteins in one analysis and without using laboratory animals (antibodies for 39 immunolocalization of single proteins). Secondly, this study offers the first complex proteomic 40 data on not only the E. nipponicum but within the whole class of Monogenea, which was from 41 this point of view until recently neglected. 42 3 43 Introduction 44 Laser-capture microdissection (LCM) was developed as a powerful and reliable tool to 45 overcome the heterogeneity of the specimen [1]. It enables isolation of specific tissues, 46 individual cells, or even individual organelles from complex samples based on cell morphology 47 [2,3]. The method was first described in the second half of the 20 th century and since then further 48 developed and modified [2,4-7]. Nowadays, LCM combines laser excision with high-resolution 49 microscopic control, which makes it possible to precisely capture for instance individual cells 50 or even only nucleus while keeping track of the location and morphology of the source tissue 51 [2,3,8]. 52 LCM technology has been used in a wide variety of applications with focus on genomic, 53 transcriptomic, and even proteomic analyses, such as dissection of polar bodies from oocytes 54 for pre-fertilization genetic diagnosis [9], transcriptome-wide analysis of blood vessels from 55 human skin and wound-edge tissue [10], proteomic profiling of dentoalveolar tissues [11], and 56 many other areas [12-14]. But only one study so far used a combination of LCM and mass 57 spectrometry (MS) to localize unique proteins, potential biomarkers, when dealing with the 58 heterogeneity of breast tumor [15]. 59 LCM has also been used in parasitology, especially in sample preparation. Recent 60 studies employed this method in...

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Transcriptional profiling of the oesophageal gland region of male worms of Schistosoma mansoni

Cited by 19 publications

References 31 publications

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

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

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Laser capture microdissection in combination with mass spectrometry: Approach to characterization of tissue-specific proteomes ofEudiplozoon nipponicum(Monogenea, Polyopisthocotylea)

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