Schistosoma mansoni: Germ-line transformation approaches and actin-promoter analysis

Beckmann, Svenja; Wippersteg, Volker; El-Bahay, Akram; Hirzmann, Jörg; Oliveira, Guilherme; Grevelding, Christoph G.

doi:10.1016/j.exppara.2007.04.007

Cited by 37 publications

(55 citation statements)

References 45 publications

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“…Our analysis testing the strength of endogenous promoters is consistent with gene expression profiles. SmActin1, which participates in cytoskeleton organization, muscle contraction, motility and morphogenesis, is ubiquitously expressed in muscle and tegument cells at all life stages [27], [30], [31]. Supporting this, we found its promoter has the highest transcription levels (Figure 2).…”

Section: Discussionsupporting

confidence: 67%

“…CMV and SV40 viral promoters are commonly used in mammalian transgenesis and have relatively high transcriptional outputs across various species [29]. The SmHsp70 and SmActin promoters direct the transcription of proteins that are ubiquitously expressed [15], [27], [30], [31], whereas both Sm23 and SmCalcineurin A generally do so for cell specific proteins [17], [32].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Schistosome Promoter Expression for Transgenesis and Genetic Analysis

et al. 2014

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Schistosome worms of the genus Schistosoma are the causative agents of schistosomiasis, a devastating parasitic disease affecting more than 240 million people worldwide. Schistosomes have complex life cycles, and have been challenging to manipulate genetically due to the dearth of molecular tools. Although the use of gene overexpression, gene knockouts or knockdowns are straight-forward genetic tools applied in many model systems, gene misexpression and genetic manipulation of schistosome genes in vivo has been exceptionally challenging, and plasmid based transfection inducing gene expression is limited. We recently reported the use of polyethyleneimine (PEI) as a simple and effective method for schistosome transfection and gene expression. Here, we use PEI-mediated schistosome plasmid transgenesis to define and compare gene expression profiles from endogenous and nonendogenous promoters in the schistosomula stage of schistosomes that are potentially useful to misexpress (underexpress or overexpress) gene product levels. In addition, we overexpress schistosome genes in vivo using a strong promoter and show plasmid-based misregulation of genes in schistosomes, producing a clear and distinct phenotype- death. These data focus on the schistosomula stage, but they foreshadow strong potential for genetic characterization of schistosome molecular pathways, and potential for use in overexpression screens and drug resistance studies in schistosomes using plasmid-based gene expression.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Evaluation of Schistosome Promoter Expression for Transgenesis and Genetic Analysis

et al. 2014

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“…The complex genomic landscape of NSCLC related to tobacco smoking is characterized by innumerable single-nucleotide variations, gene amplifications, insertions, deletions, and structural rearrangements ( 12,13). By contrast, there are strikingly fewer mutations and genomic alterations in the lung cancer specimens from nonsmokers ( 14).…”

Section: Attack Of the Clonesmentioning

confidence: 96%

Halting harmful helminths

Hoffmann

Brindley

Berriman

2014

Science

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More than 300 million people are infected each year with parasitic flatworms such as hydatid tapeworms and blood fluke schistosomes. The diseases caused by such parasitic helminths, including alveolar/cystic echinococcosis and hepatosplenic/urogenital schistosomiasis, are typically chronic but frequently deadly. They are among the 17 neglected tropical diseases listed by the United Nations World Health Organization, and infections by these flatworm pathogens cause ?4 million disability-adjusted life years to be lost annually, although this vastly underestimates the true impact that such long-term and chronic illnesses can have (1). Historically considered restricted to the tropics and subtropics, suitable habitats for transmission of these parasites are now expanding into Europe (2), and conditions are right for similar expansions to other continents (3, 4). The lack of vaccines perpetuates the unsustainable over-reliance on single-drug chemotherapies, a potentially catastrophic situation unless new solutions are found

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“…However, these tools have not been thoroughly developed for use in developing or mature cercariae. Our group and others are working on developing methods to overcome these technical challenges [74–79]. Analysis in cercariae is challenging, as cercariae are short lived, transient, and the necessary proteins for swimming and host invasion have already been produced prior to exit from the snail host.…”

Section: Discussionmentioning

confidence: 99%

Hsp70 May Be a Molecular Regulator of Schistosome Host Invasion

Ishida

Jolly

2016

PLoS Negl Trop Dis

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Schistosomiasis is a debilitating disease that affects over 240 million people worldwide and is considered the most important neglected tropical disease following malaria. Free-swimming freshwater cercariae, one of the six morphologically distinct schistosome life stages, infect humans by directly penetrating through the skin. Cercariae identify and seek the host by sensing chemicals released from human skin. When they reach the host, they burrow into the skin with the help of proteases and other contents released from their acetabular glands and transform into schistosomula, the subsequent larval worm stage upon skin infection. Relative to host invasion, studies have primarily focused on the nature of the acetabular gland secretions, immune response of the host upon exposure to cercariae, and cercaria-schistosomulum transformation methods. However, the molecular signaling pathways involved from host-seeking through the decision to penetrate skin are not well understood. We recently observed that heat shock factor 1 (Hsf1) is localized to the acetabular glands of infectious schistosome cercariae, prompting us to investigate a potential role for heat shock proteins (HSPs) in cercarial invasion. In this study, we report that cercarial invasion behavior, similar to the behavior of cercariae exposed to human skin lipid, is regulated through an Hsp70-dependent process, which we show by using chemical agents that target Hsp70. The observation that biologically active protein activity modulators can elicit a direct and clear behavioral change in parasitic schistosome larvae is itself interesting and has not been previously observed. This finding suggests a novel role for Hsp70 to act as a switch in the cercaria-schistosomulum transformation, and it allows us to begin elucidating the pathways associated with cercarial host invasion. In addition, because the Hsp70 protein and its structure/function is highly conserved, the model that Hsp70 acts as a behavior transitional switch could be relevant to other parasites that also undergo an invasion process and can apply more broadly to other organisms during morphological transitions. Finally, it points to a new function for HSPs in parasite/host interactions.

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Schistosoma mansoni: Germ-line transformation approaches and actin-promoter analysis

Cited by 37 publications

References 45 publications

Evaluation of Schistosome Promoter Expression for Transgenesis and Genetic Analysis

Evaluation of Schistosome Promoter Expression for Transgenesis and Genetic Analysis

Halting harmful helminths

Hsp70 May Be a Molecular Regulator of Schistosome Host Invasion

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