2024-03-28T10:21:16Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/88262023-07-27T01:00:52Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
Repisalud
author
Tedla, Bemnet A
author
Sotillo, Javier
author
Pickering, Darren
author
Eichenberger, Ramon M
author
Ryan, Stephanie
author
Becker, Luke
author
Loukas, Alex
author
Pearson, Mark S
2019-12-12T08:55:07Z
2019-12-12T08:55:07Z
2019-12-06
PLoS Pathog. 2019 Dec 6;15(12):e1008213.
1553-7374
http://hdl.handle.net/20.500.12105/8826
31809524
10.1371/journal.ppat.1008213
1553-7374
PLoS pathogens
Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain-containing genes (Smche)s, which we have shown to encode two functional acetylcholinesterases (AChE)s (Smache1 -smp_154600 and Smache2 -smp_136690) and a butyrylcholinesterase (BChE) (Smbche1 -smp_125350). Antibodies to recombinant forms of each SmChE localized the proteins to the tegument of adults and schistosomula and developmental expression profiling differed among the three molecules, suggestive of functions extending beyond traditional cholinergic signaling. For the first time in schistosomes, we identified ChE enzymatic activity in fluke excretory/secretory (ES) products and, using proteomic approaches, attributed this activity to the presence of SmAChE1 and SmBChE1. Parasite survival in vitro and in vivo was significantly impaired by silencing of each smche, either individually or in combination, attesting to the essential roles of these molecules. Lastly, in the first characterization study of a BChE from helminths, evidence is provided that SmBChE1 may act as a bio-scavenger of AChE inhibitors as the addition of recombinant SmBChE1 to parasite cultures mitigated the effect of the anti-schistosome AChE inhibitor 2,2- dichlorovinyl dimethyl phosphate-dichlorvos (DDVP), whereas smbche1-silenced parasites displayed increased sensitivity to DDVP.
eng
Novel cholinesterase paralogs of Schistosoma mansoni have perceived roles in cholinergic signaling and drug detoxification and are essential for parasite survival
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/8826/8/NovelCholinesteraseParalogsSchistosoma_2019.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/8826/7/NovelCholinesteraseParalogsOf_2019.pdf.txt
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NovelCholinesteraseParalogsOf_2019.pdf.txt
URL
https://repisalud.isciii.es/bitstream/20.500.12105/8826/9/NovelCholinesteraseParalogsSchistosoma_2019.pdf.txt
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NovelCholinesteraseParalogsSchistosoma_2019.pdf.txt