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      A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host

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          Abstract

          Schistosomes are parasitic flatworms that infect over 200 million people, causing the neglected tropical disease, schistosomiasis. A single drug, praziquantel, is used to treat schistosome infection. Limitations in mass drug administration programs and the emergence of schistosomiasis in nontropical areas indicate the need for new strategies to prevent infection. It has been known for several decades that rotifers colonizing the schistosome's snail intermediate host produce a water-soluble factor that paralyzes cercariae, the life cycle stage infecting humans. In spite of its potential for preventing infection, the nature of this factor has remained obscure. Here, we report the purification and chemical characterization of Schistosome Paralysis Factor (SPF), a novel tetracyclic alkaloid produced by the rotifer Rotaria rotatoria. We show that this compound paralyzes schistosome cercariae and prevents infection and does so more effectively than analogous compounds. This molecule provides new directions for understanding cercariae motility and new strategies for preventing schistosome infection.

          Abstract

          Commensal rotifers living on the intermediate host (snail) of a human parasite (schistosome) produce a factor that paralyzes the schistosome's infective larvae and prevents them from infecting a mammalian definitive host (mouse). Identification of this molecule provides new directions for understanding larval motility and new strategies for preventing schistosome infection.

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          Most cited references33

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            A New Golden Age of Natural Products Drug Discovery.

            Ben Shen (2015)
            The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning.
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              Massive horizontal gene transfer in bdelloid rotifers.

              Horizontal gene transfer in metazoans has been documented in only a few species and is usually associated with endosymbiosis or parasitism. By contrast, in bdelloid rotifers we found many genes that appear to have originated in bacteria, fungi, and plants, concentrated in telomeric regions along with diverse mobile genetic elements. Bdelloid proximal gene-rich regions, however, appeared to lack foreign genes, thereby resembling those of model metazoan organisms. Some of the foreign genes were defective, whereas others were intact and transcribed; some of the latter contained functional spliceosomal introns. One such gene, apparently of bacterial origin, was overexpressed in Escherichia coli and yielded an active enzyme. The capture and functional assimilation of exogenous genes may represent an important force in bdelloid evolution.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                17 October 2019
                October 2019
                17 October 2019
                : 17
                : 10
                : e3000485
                Affiliations
                [1 ] Cellular and Molecular Biology Program, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                [2 ] Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [3 ] Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [4 ] Biomedical Research Institute, Rockville, Maryland, United States of America
                [5 ] Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [6 ] Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America
                [7 ] Morgridge Institute for Research, Madison, Wisconsin, United States of America
                [8 ] Department of Integrative Biology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                Stanford University, UNITED STATES
                Author notes

                I have read the journal's policy and the authors of this manuscript have the following competing interest: A patent application has been filed by the Wisconsin Alumni Research Foundation and is pending. Use of a Rotifer-Derived Compound and its Analogs for Preventing Schistosomiasis. US Application #: 16/445766, covers the use of this novel molecule and its derivatives in preventing schistosome infection.

                [¤a]

                Current address: Bernville, Pennsylvania, United States of America

                [¤b]

                Current address: Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas, United States of America

                Author information
                http://orcid.org/0000-0003-3447-5816
                http://orcid.org/0000-0002-1984-185X
                http://orcid.org/0000-0003-3107-9922
                http://orcid.org/0000-0003-0793-022X
                Article
                PBIOLOGY-D-19-01881
                10.1371/journal.pbio.3000485
                6797223
                31622335
                208fcc5b-ab56-4891-881f-8c115cf9b7a0
                © 2019 Gao et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 July 2019
                : 13 September 2019
                Page count
                Figures: 4, Tables: 0, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award ID: Investigator Award
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award ID: International Student Research Fellowship
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000026, National Institute on Drug Abuse;
                Award ID: P30 DA018310
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: R01 NS031609
                Award Recipient :
                This work was supported by: Howard Hughes Medical Institute ( https://www.hhmi.org/): Investigator Award to PAN; International Student Research Fellowship to JG; National Institute of Neurological Diseases and Stroke ( https://www.ninds.nih.gov/): R01 NS031609 to JVS; National Institute on Drug Abuse ( https://www.drugabuse.gov/): P30 DA018310 to JVS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Short Reports
                Physical Sciences
                Physics
                Nuclear Physics
                Nucleons
                Protons
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Research and analysis methods
                Spectrum analysis techniques
                NMR spectroscopy
                Biology and Life Sciences
                Organisms
                Eukaryota
                Rotifers
                Research and analysis methods
                Spectrum analysis techniques
                NMR spectroscopy
                Nuclear Overhauser effect spectroscopy
                Research and analysis methods
                Spectrum analysis techniques
                NMR spectroscopy
                Correlation Spectroscopy
                Medicine and Health Sciences
                Parasitic Diseases
                Research and analysis methods
                Spectrum analysis techniques
                NMR spectroscopy
                Heteronuclear Single Quantum Coherence Spectroscopy
                Custom metadata
                The data files for NMR, LC-MS, MALDI MS and H/D exchange MS have been deposited into Illinois DataBank. DOI: https://doi.org/10.13012/B2IDB-1599850_V1.

                Life sciences
                Life sciences

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