The effects of plant cysteine proteinases on the nematode cuticle

NJOM, Victor S., WINKS, Tim, DIALLO, Oumu, LOWE, Ann, BEHNKE, Jerzy, DICKMAN, Mark J., DUCE, Ian, JOHNSTONE, Iain and BUTTLE, David J. (2021). The effects of plant cysteine proteinases on the nematode cuticle. Parasites & Vectors, 14 (1).

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Official URL: https://parasitesandvectors.biomedcentral.com/arti...
Open Access URL: https://parasitesandvectors.biomedcentral.com/trac... (Published version)
Link to published version:: https://doi.org/10.1186/s13071-021-04800-8
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    Abstract

    Abstract: Background: Plant-derived cysteine proteinases of the papain family (CPs) attack nematodes by digesting the cuticle, leading to rupture and death of the worm. The nematode cuticle is composed of collagens and cuticlins, but the specific molecular target(s) for the proteinases have yet to be identified. Methods: This study followed the course of nematode cuticle disruption using immunohistochemistry, scanning electron microscopy and proteomics, using a free-living nematode, Caenorhabditis elegans and the murine GI nematode Heligmosomoides bakeri (H. polygyrus) as target organisms. Results: Immunohistochemistry indicated that DPY-7 collagen is a target for CPs on the cuticle of C. elegans. The time course of loss of DPY-7 from the cuticle allowed us to use it to visualise the process of cuticle disruption. There was a marked difference in the time course of damage to the cuticles of the two species of nematode, with H. bakeri being more rapidly hydrolysed. In general, the CPs’ mode of attack on the nematode cuticle was by degrading the structural proteins, leading to loss of integrity of the cuticle, and finally death of the nematode. Proteomic analysis failed conclusively to identify structural targets for CPs, but preliminary data suggested that COL-87 and CUT-19 may be important targets for the CPs, the digestion of which may contribute to cuticle disruption and death of the worm. Cuticle globin was also identified as a cuticular target. The presence of more than one target protein may slow the development of resistance against this new class of anthelmintic. Conclusions: Scanning electron microscopy and immunohistochemistry allowed the process of disruption of the cuticle to be followed with time. Cuticle collagens and cuticlins are molecular targets for plant cysteine proteinases. However, the presence of tyrosine cross-links in nematode cuticle proteins seriously impeded protein identification by proteomic analyses. Multiple cuticle targets exist, probably making resistance to this new anthelmintic slow to develop. Graphic Abstract:

    Item Type: Article
    Additional Information: ** From Springer Nature via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1756-3305 **Article IDs: publisher-id: s13071-021-04800-8; manuscript: 4800 **History: collection 12-2021; online 05-06-2021; published 05-06-2021; registration 24-05-2021; accepted 24-05-2021; submitted 05-04-2021
    Uncontrolled Keywords: Research, Helminths and helminthic diseases, C. elegans, H. bakeri, Papain, Papaya latex, Cuticle, Anthelmintic, Proteomics, Imaging, Immunohistochemistry
    Identification Number: https://doi.org/10.1186/s13071-021-04800-8
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 07 Jun 2021 10:48
    Last Modified: 07 Jun 2021 11:00
    URI: http://shura.shu.ac.uk/id/eprint/28719

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