1. Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites
- Author
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Christoph Grunau, Guillaume Tetreau, Marie-Laure Walet-Balieu, Philippe Chan, Ronaldo de Carvalho Augusto, Clélia Christina Mello-Silva, Cláudia Portes Santos, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This study received funding from Wellcome Trust (Flatworm Functional Genomics Initiative (FUGI) - 107475/Z/15/Z), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES Parasitologia Básica/2011), Fundação Carlos Chagas Filho de Amparo à Pesquisa no Rio de Janeiro (FAPERJ–BIOTA 2012), Conselho Nacional de Pesquisa (CNPq) – Edital Universal 2014 and PAEF/Fiocruz (PAEF no. IOC-008-FIO-04), CNPq fellowships (205872/2014-0 – SWE) and MATER-IMMUNITY Project (ANR-14-CE02-0009) of the French National Research Agency (ANR).
- Subjects
Male ,0301 basic medicine ,Schistosoma Mansoni ,Latex ,Euphorbia milii ,Gene Expression ,Biomphalaria ,Pathogenesis ,MESH: Latex/administration & dosage ,Pathology and Laboratory Medicine ,Biochemistry ,Parasite load ,Parasite Load ,MESH: Linear Models ,Mice ,0302 clinical medicine ,Animal Cells ,MESH: Sequence Analysis, RNA ,Medicine and Health Sciences ,Schistosomiasis ,Parasite hosting ,MESH: Animals ,MESH: Cercaria/growth & development ,Cercaria ,MESH: Molluscacides/administration & dosage ,biology ,lcsh:Public aspects of medicine ,3. Good health ,MESH: Schistosoma mansoni/drug effects ,Praziquantel ,Infectious Diseases ,Liver ,Helminth Infections ,Molluscicide ,Physical Sciences ,Host-Pathogen Interactions ,Granulomas ,Schistosoma ,Emulsions ,Female ,Metabolic Pathways ,Schistosoma mansoni ,MESH: Cercaria/drug effects ,Cellular Types ,Brazil ,Research Article ,Neglected Tropical Diseases ,medicine.drug ,lcsh:Arctic medicine. Tropical medicine ,Molluscacides ,lcsh:RC955-962 ,Materials by Structure ,Immune Cells ,Materials Science ,Immunology ,030231 tropical medicine ,MESH: Microscopy, Electron ,MESH: Liver/pathology ,MESH: Schistosoma mansoni/ultrastructure ,03 medical and health sciences ,Helminths ,parasitic diseases ,Parasitic Diseases ,Genetics ,medicine ,Animals ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Colloids ,MESH: Mice ,MESH: Biomphalaria/parasitology ,Plant Extracts ,Sequence Analysis, RNA ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,lcsh:RA1-1270 ,Cell Biology ,MESH: Schistosomiasis mansoni/parasitology ,Tropical Diseases ,biology.organism_classification ,medicine.disease ,Invertebrates ,MESH: Male ,Schistosomiasis mansoni ,MESH: Parasite Load ,Microscopy, Electron ,Metabolism ,030104 developmental biology ,Mixtures ,Linear Models ,MESH: Schistosomiasis mansoni/prevention & control ,MESH: Plant Extracts/administration & dosage ,MESH: Brazil ,MESH: Female - Abstract
Background Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite’s biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite’s life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts. Methodology/Principal findings We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics. Conclusions/Significance We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection)., Author summary Intestinal schistosomiasis is among the most important parasitic disease caused by helminthes, affecting 67 million people worldwide. Vector and intermediate host of the parasitic worm are fresh water snails. WHO recommends use of molluscicides for control of local transmission. Among those, natural plant extracts such as Euphorbia milii latex have attracted particular attention since they are sustainable and cheap. We had anecdotic evidence that E. milii latex also impacts infection outcome if treated snails were infected with S. mansoni. We show here that transient exposure of the human dwelling larvae (cercariae) to the latex at doses that do not affect its infectivity has effects 60 days later on the morphology, physiology and fitness of the adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics. We show that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. The present work might also provide insights on targets with implications for developing new interventions for schistosomiasis control.
- Published
- 2017