Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens.
Miltefosine, an anti-cancer drug that has been successfully repositioned for treatment of Leishmania infections, has recently also shown promising effects against Schistosoma spp targeting all life cycle stages of the parasite. The current study examined the effect of treating Schistosoma mansoni ad...
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ftdoajarticles:oai:doaj.org/article:71baeeda75804683bf1f2ae2cbb330c6 2023-05-15T15:16:14+02:00 Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. Marwa H El-Faham Maha M Eissa Joseph E Igetei Eglal I Amer Susan Liddell Mervat Z El-Azzouni Michael J Doenhoff 2017-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005853 https://doaj.org/article/71baeeda75804683bf1f2ae2cbb330c6 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5589257?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005853 https://doaj.org/article/71baeeda75804683bf1f2ae2cbb330c6 PLoS Neglected Tropical Diseases, Vol 11, Iss 8, p e0005853 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005853 2022-12-31T13:35:31Z Miltefosine, an anti-cancer drug that has been successfully repositioned for treatment of Leishmania infections, has recently also shown promising effects against Schistosoma spp targeting all life cycle stages of the parasite. The current study examined the effect of treating Schistosoma mansoni adult worms with miltefosine on exposure of worm surface antigens in vitro.In an indirect immunofluorescence assay, rabbit anti-S.mansoni adult worm homogenate and anti-S. mansoni infection antisera gave strong immunofluorescence of the S. mansoni adult worm surface after treatment with miltefosine, the latter antiserum having previously been shown to synergistically enhance the schistosomicidal activity of praziquantel. Rabbit antibodies that recognised surface antigens exposed on miltefosine-treated worms were recovered by elution off the worm surface in low pH buffer and were used in a western immunoblotting assay to identify antigenic targets in a homogenate extract of adult worms (SmWH). Four proteins reacting with the antibodies in immunoblots were purified and proteomic analysis (MS/MS) combined with specific immunoblotting indicated they were the S. mansoni proteins: fructose-1,6 bisphosphate aldolase (SmFBPA), Sm22.6, alkaline phosphatase and malate dehydrogenase. These antibodies were also found to bind to the surface of 3-hour schistosomula and induce immune agglutination of the parasites, suggesting they may have a role in immune protection.This study reveals a novel mode of action of miltefosine as an anti-schistosome agent. The immune-dependent hypothesis we investigated has previously been lent credence with praziquantel (PZQ), whereby treatment unmasks parasite surface antigens not normally exposed to the host during infection. Antigens involved in this molecular mechanism could have potential as intervention targets and antibodies against these antigens may act to increase the drug's anti-parasite efficacy and be involved in the development of resistance to re-infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Lent ENVELOPE(-66.783,-66.783,-66.867,-66.867) PLOS Neglected Tropical Diseases 11 8 e0005853 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Marwa H El-Faham Maha M Eissa Joseph E Igetei Eglal I Amer Susan Liddell Mervat Z El-Azzouni Michael J Doenhoff Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Miltefosine, an anti-cancer drug that has been successfully repositioned for treatment of Leishmania infections, has recently also shown promising effects against Schistosoma spp targeting all life cycle stages of the parasite. The current study examined the effect of treating Schistosoma mansoni adult worms with miltefosine on exposure of worm surface antigens in vitro.In an indirect immunofluorescence assay, rabbit anti-S.mansoni adult worm homogenate and anti-S. mansoni infection antisera gave strong immunofluorescence of the S. mansoni adult worm surface after treatment with miltefosine, the latter antiserum having previously been shown to synergistically enhance the schistosomicidal activity of praziquantel. Rabbit antibodies that recognised surface antigens exposed on miltefosine-treated worms were recovered by elution off the worm surface in low pH buffer and were used in a western immunoblotting assay to identify antigenic targets in a homogenate extract of adult worms (SmWH). Four proteins reacting with the antibodies in immunoblots were purified and proteomic analysis (MS/MS) combined with specific immunoblotting indicated they were the S. mansoni proteins: fructose-1,6 bisphosphate aldolase (SmFBPA), Sm22.6, alkaline phosphatase and malate dehydrogenase. These antibodies were also found to bind to the surface of 3-hour schistosomula and induce immune agglutination of the parasites, suggesting they may have a role in immune protection.This study reveals a novel mode of action of miltefosine as an anti-schistosome agent. The immune-dependent hypothesis we investigated has previously been lent credence with praziquantel (PZQ), whereby treatment unmasks parasite surface antigens not normally exposed to the host during infection. Antigens involved in this molecular mechanism could have potential as intervention targets and antibodies against these antigens may act to increase the drug's anti-parasite efficacy and be involved in the development of resistance to re-infection. |
format |
Article in Journal/Newspaper |
author |
Marwa H El-Faham Maha M Eissa Joseph E Igetei Eglal I Amer Susan Liddell Mervat Z El-Azzouni Michael J Doenhoff |
author_facet |
Marwa H El-Faham Maha M Eissa Joseph E Igetei Eglal I Amer Susan Liddell Mervat Z El-Azzouni Michael J Doenhoff |
author_sort |
Marwa H El-Faham |
title |
Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
title_short |
Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
title_full |
Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
title_fullStr |
Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
title_full_unstemmed |
Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
title_sort |
treatment of schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005853 https://doaj.org/article/71baeeda75804683bf1f2ae2cbb330c6 |
long_lat |
ENVELOPE(-66.783,-66.783,-66.867,-66.867) |
geographic |
Arctic Lent |
geographic_facet |
Arctic Lent |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 8, p e0005853 (2017) |
op_relation |
http://europepmc.org/articles/PMC5589257?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005853 https://doaj.org/article/71baeeda75804683bf1f2ae2cbb330c6 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005853 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
8 |
container_start_page |
e0005853 |
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1766346527618367488 |