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Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7

BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during...

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Autores principales: Reimers, Natalie, Homann, Arne, Höschler, Beate, Langhans, Kristina, Wilson, R. Alan, Pierrot, Christine, Khalife, Jamal, Grevelding, Christoph G., Chalmers, Iain W., Yazdanbakhsh, Maria, Hoffmann, Karl F., Hokke, Cornelis H., Haas, Helmut, Schramm, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361651/
https://www.ncbi.nlm.nih.gov/pubmed/25774883
http://dx.doi.org/10.1371/journal.pntd.0003593
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author Reimers, Natalie
Homann, Arne
Höschler, Beate
Langhans, Kristina
Wilson, R. Alan
Pierrot, Christine
Khalife, Jamal
Grevelding, Christoph G.
Chalmers, Iain W.
Yazdanbakhsh, Maria
Hoffmann, Karl F.
Hokke, Cornelis H.
Haas, Helmut
Schramm, Gabriele
author_facet Reimers, Natalie
Homann, Arne
Höschler, Beate
Langhans, Kristina
Wilson, R. Alan
Pierrot, Christine
Khalife, Jamal
Grevelding, Christoph G.
Chalmers, Iain W.
Yazdanbakhsh, Maria
Hoffmann, Karl F.
Hokke, Cornelis H.
Haas, Helmut
Schramm, Gabriele
author_sort Reimers, Natalie
collection PubMed
description BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages. CONCLUSION: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack.
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spelling pubmed-43616512015-03-23 Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7 Reimers, Natalie Homann, Arne Höschler, Beate Langhans, Kristina Wilson, R. Alan Pierrot, Christine Khalife, Jamal Grevelding, Christoph G. Chalmers, Iain W. Yazdanbakhsh, Maria Hoffmann, Karl F. Hokke, Cornelis H. Haas, Helmut Schramm, Gabriele PLoS Negl Trop Dis Research Article BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages. CONCLUSION: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack. Public Library of Science 2015-03-16 /pmc/articles/PMC4361651/ /pubmed/25774883 http://dx.doi.org/10.1371/journal.pntd.0003593 Text en © 2015 Reimers et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Reimers, Natalie
Homann, Arne
Höschler, Beate
Langhans, Kristina
Wilson, R. Alan
Pierrot, Christine
Khalife, Jamal
Grevelding, Christoph G.
Chalmers, Iain W.
Yazdanbakhsh, Maria
Hoffmann, Karl F.
Hokke, Cornelis H.
Haas, Helmut
Schramm, Gabriele
Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title_full Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title_fullStr Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title_full_unstemmed Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title_short Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7
title_sort drug-induced exposure of schistosoma mansoni antigens smcd59a and smkk7
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361651/
https://www.ncbi.nlm.nih.gov/pubmed/25774883
http://dx.doi.org/10.1371/journal.pntd.0003593
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