Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes.
Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while...
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ftdoajarticles:oai:doaj.org/article:ece6ce0ee0f34df2b0b6fc753030740b 2023-05-15T15:16:25+02:00 Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. Lisa H Verzier Rachael Coyle Shivani Singh Theo Sanderson Julian C Rayner 2019-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007470 https://doaj.org/article/ece6ce0ee0f34df2b0b6fc753030740b EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007470 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007470 https://doaj.org/article/ece6ce0ee0f34df2b0b6fc753030740b PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007470 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007470 2022-12-31T10:07:30Z Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while some molecular markers of resistance have been identified, none have so far been confirmed experimentally, which limits interpretation of the markers, and hence our ability to monitor and control the spread of resistance. Some of these potential markers have been identified through P. vivax genome-wide population genetic analyses, which highlighted genes under recent evolutionary selection in Southeast Asia, where chloroquine resistance is most prevalent. These genes could be involved in drug resistance, but no experimental proof currently exists to support this hypothesis. In this study, we used Plasmodium knowlesi, the most closely related species to P. vivax that can be cultured in human erythrocytes, as a model system to express P. vivax genes and test for their role in drug resistance. We adopted a strategy of episomal expression, and were able to express fourteen P. vivax genes, including two allelic variants of several hypothetical resistance genes. Their expression level and localisation were assessed, confirming cellular locations conjectured from orthologous species, and suggesting locations for several previously unlocalised proteins, including an apical location for PVX_101445. These findings establish P. knowlesi as a suitable model for P. vivax protein expression. We performed chloroquine and mefloquine drug assays, finding no significant differences in drug sensitivity: these results could be due to technical issues, or could indicate that these genes are not actually involved in drug resistance, despite being under positive selection pressure in Southeast Asia. These data confirm that in vitro P. knowlesi is a useful tool for studying P. vivax biology. Its close evolutionary relationship to P. vivax, ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 6 e0007470 |
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Directory of Open Access Journals: DOAJ Articles |
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language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Lisa H Verzier Rachael Coyle Shivani Singh Theo Sanderson Julian C Rayner Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while some molecular markers of resistance have been identified, none have so far been confirmed experimentally, which limits interpretation of the markers, and hence our ability to monitor and control the spread of resistance. Some of these potential markers have been identified through P. vivax genome-wide population genetic analyses, which highlighted genes under recent evolutionary selection in Southeast Asia, where chloroquine resistance is most prevalent. These genes could be involved in drug resistance, but no experimental proof currently exists to support this hypothesis. In this study, we used Plasmodium knowlesi, the most closely related species to P. vivax that can be cultured in human erythrocytes, as a model system to express P. vivax genes and test for their role in drug resistance. We adopted a strategy of episomal expression, and were able to express fourteen P. vivax genes, including two allelic variants of several hypothetical resistance genes. Their expression level and localisation were assessed, confirming cellular locations conjectured from orthologous species, and suggesting locations for several previously unlocalised proteins, including an apical location for PVX_101445. These findings establish P. knowlesi as a suitable model for P. vivax protein expression. We performed chloroquine and mefloquine drug assays, finding no significant differences in drug sensitivity: these results could be due to technical issues, or could indicate that these genes are not actually involved in drug resistance, despite being under positive selection pressure in Southeast Asia. These data confirm that in vitro P. knowlesi is a useful tool for studying P. vivax biology. Its close evolutionary relationship to P. vivax, ... |
format |
Article in Journal/Newspaper |
author |
Lisa H Verzier Rachael Coyle Shivani Singh Theo Sanderson Julian C Rayner |
author_facet |
Lisa H Verzier Rachael Coyle Shivani Singh Theo Sanderson Julian C Rayner |
author_sort |
Lisa H Verzier |
title |
Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
title_short |
Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
title_full |
Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
title_fullStr |
Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
title_full_unstemmed |
Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes. |
title_sort |
plasmodium knowlesi as a model system for characterising plasmodium vivax drug resistance candidate genes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007470 https://doaj.org/article/ece6ce0ee0f34df2b0b6fc753030740b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007470 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007470 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007470 https://doaj.org/article/ece6ce0ee0f34df2b0b6fc753030740b |
op_doi |
https://doi.org/10.1371/journal.pntd.0007470 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
6 |
container_start_page |
e0007470 |
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