Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites.
Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008465 |
| _version_ | 1818926844188033024 |
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| author | Charlotte A Scarff Rebecca F Thompson George F J Newlands Alexander H Jamson Christopher Kennaway Vivian J da Silva Elida M Rabelo Chun-Feng Song John Trinick W David Smith Stephen P Muench |
| author_facet | Charlotte A Scarff Rebecca F Thompson George F J Newlands Alexander H Jamson Christopher Kennaway Vivian J da Silva Elida M Rabelo Chun-Feng Song John Trinick W David Smith Stephen P Muench |
| author_sort | Charlotte A Scarff |
| collection | DOAJ |
| description | Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'hidden antigens', components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber's Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine. |
| first_indexed | 2024-12-20T03:03:34Z |
| format | Article |
| id | doaj.art-0ff427ede1274c4cb57f1665bf1bf24f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-20T03:03:34Z |
| publishDate | 2020-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0ff427ede1274c4cb57f1665bf1bf24f2022-12-21T19:55:39ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-04-01164e100846510.1371/journal.ppat.1008465Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites.Charlotte A ScarffRebecca F ThompsonGeorge F J NewlandsAlexander H JamsonChristopher KennawayVivian J da SilvaElida M RabeloChun-Feng SongJohn TrinickW David SmithStephen P MuenchRoundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and 'hidden antigens', components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber's Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.https://doi.org/10.1371/journal.ppat.1008465 |
| spellingShingle | Charlotte A Scarff Rebecca F Thompson George F J Newlands Alexander H Jamson Christopher Kennaway Vivian J da Silva Elida M Rabelo Chun-Feng Song John Trinick W David Smith Stephen P Muench Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. PLoS Pathogens |
| title | Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. |
| title_full | Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. |
| title_fullStr | Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. |
| title_full_unstemmed | Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. |
| title_short | Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites. |
| title_sort | structure of the protective nematode protease complex h gal gp and its conservation across roundworm parasites |
| url | https://doi.org/10.1371/journal.ppat.1008465 |
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