Novel cholinesterase paralogs of Schistosoma mansoni have perceived roles in cholinergic signaling and drug detoxification and are essential for parasite survival

Tedla, Bemnet A., Sotillo, Javier, Pickering, Darren, Eichenberger, Ramon M., Ryan, Stephanie, Becker, Luke, Loukas, Alex, and Pearson, Mark S. (2019) Novel cholinesterase paralogs of Schistosoma mansoni have perceived roles in cholinergic signaling and drug detoxification and are essential for parasite survival. PLoS Pathogens, 15 (12). e1008213.

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Abstract

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 domaincontaining 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.

Item ID: 62877
Item Type: Article (Research - C1)
ISSN: 1553-7374
Copyright Information: © 2019 Tedla et al. 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 credited.
Funders: National Health and Medical Research Council of Australia (NHMRC), James Cook University Postgraduate Scholarship
Projects and Grants: NHMRC APP1037304, NHMRC APP1117504
Date Deposited: 19 Apr 2020 23:17
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920412 Preventive Medicine @ 50%
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