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A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection
Schistosomes are long-lived parasitic worms that infect >200 million people globally. The intravascular life stages are known to display acetylcholinesterase (AChE) activity internally as well as, somewhat surprisingly, on external tegumental membranes. Originally it was hypothesized that a singl...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927205/ https://www.ncbi.nlm.nih.gov/pubmed/36798133 http://dx.doi.org/10.3389/fimmu.2023.1056469 |
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author | Skelly, Patrick J. Da’dara, Akram A. |
author_facet | Skelly, Patrick J. Da’dara, Akram A. |
author_sort | Skelly, Patrick J. |
collection | PubMed |
description | Schistosomes are long-lived parasitic worms that infect >200 million people globally. The intravascular life stages are known to display acetylcholinesterase (AChE) activity internally as well as, somewhat surprisingly, on external tegumental membranes. Originally it was hypothesized that a single gene (SmAChE1 in Schistosoma mansoni) encoded both forms of the enzyme. Here, we demonstrate that a second gene, designated “S. mansoni tegumental acetylcholinesterase, SmTAChE”, is responsible for surface, non-neuronal AChE activity. The SmTAChE protein is GPI-anchored and contains all essential amino acids necessary for function. AChE surface activity is significantly diminished following SmTAChE gene suppression using RNAi, but not following SmAChE1 gene suppression. Suppressing SmTAChE significantly impairs the ability of parasites to establish infection in mice, showing that SmTAChE performs an essential function for the worms in vivo. Living S. haematobium and S. japonicum parasites also display strong surface AChE activity, and we have cloned SmTAChE homologs from these two species. This work helps to clarify longstanding confusion regarding schistosome AChEs and paves the way for novel therapeutics for schistosomiasis. |
format | Online Article Text |
id | pubmed-9927205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99272052023-02-15 A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection Skelly, Patrick J. Da’dara, Akram A. Front Immunol Immunology Schistosomes are long-lived parasitic worms that infect >200 million people globally. The intravascular life stages are known to display acetylcholinesterase (AChE) activity internally as well as, somewhat surprisingly, on external tegumental membranes. Originally it was hypothesized that a single gene (SmAChE1 in Schistosoma mansoni) encoded both forms of the enzyme. Here, we demonstrate that a second gene, designated “S. mansoni tegumental acetylcholinesterase, SmTAChE”, is responsible for surface, non-neuronal AChE activity. The SmTAChE protein is GPI-anchored and contains all essential amino acids necessary for function. AChE surface activity is significantly diminished following SmTAChE gene suppression using RNAi, but not following SmAChE1 gene suppression. Suppressing SmTAChE significantly impairs the ability of parasites to establish infection in mice, showing that SmTAChE performs an essential function for the worms in vivo. Living S. haematobium and S. japonicum parasites also display strong surface AChE activity, and we have cloned SmTAChE homologs from these two species. This work helps to clarify longstanding confusion regarding schistosome AChEs and paves the way for novel therapeutics for schistosomiasis. Frontiers Media S.A. 2023-01-31 /pmc/articles/PMC9927205/ /pubmed/36798133 http://dx.doi.org/10.3389/fimmu.2023.1056469 Text en Copyright © 2023 Skelly and Da’dara https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Skelly, Patrick J. Da’dara, Akram A. A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title | A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title_full | A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title_fullStr | A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title_full_unstemmed | A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title_short | A novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
title_sort | novel, non-neuronal acetylcholinesterase of schistosome parasites is essential for definitive host infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927205/ https://www.ncbi.nlm.nih.gov/pubmed/36798133 http://dx.doi.org/10.3389/fimmu.2023.1056469 |
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