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Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine
The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resis...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175063/ https://www.ncbi.nlm.nih.gov/pubmed/36478252 http://dx.doi.org/10.1093/infdis/jiac469 |
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author | Ward, Kurt E Christensen, Peter Racklyeft, Annie Dhingra, Satish K Chua, Adeline C Y Remmert, Caroline Suwanarusk, Rossarin Matheson, Jessica Blackman, Michael J Kaneko, Osamu Kyle, Dennis E Lee, Marcus C S Moon, Robert W Snounou, Georges Rénia, Laurent Fidock, David A Russell, Bruce Bifani, Pablo |
author_facet | Ward, Kurt E Christensen, Peter Racklyeft, Annie Dhingra, Satish K Chua, Adeline C Y Remmert, Caroline Suwanarusk, Rossarin Matheson, Jessica Blackman, Michael J Kaneko, Osamu Kyle, Dennis E Lee, Marcus C S Moon, Robert W Snounou, Georges Rénia, Laurent Fidock, David A Russell, Bruce Bifani, Pablo |
author_sort | Ward, Kurt E |
collection | PubMed |
description | The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F. Introduction of this mutation using clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9 (CRISPR-Cas9) increased sensitivity to mefloquine, but had no significant effect on sensitivity to chloroquine, amodiaquine, piperaquine, and artesunate. To our knowledge, this is the first reported use of CRISPR-Cas9 in P. cynomolgi, and the first reported integrative genetic manipulation of this species. |
format | Online Article Text |
id | pubmed-10175063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101750632023-05-13 Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine Ward, Kurt E Christensen, Peter Racklyeft, Annie Dhingra, Satish K Chua, Adeline C Y Remmert, Caroline Suwanarusk, Rossarin Matheson, Jessica Blackman, Michael J Kaneko, Osamu Kyle, Dennis E Lee, Marcus C S Moon, Robert W Snounou, Georges Rénia, Laurent Fidock, David A Russell, Bruce Bifani, Pablo J Infect Dis Major Article The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F. Introduction of this mutation using clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9 (CRISPR-Cas9) increased sensitivity to mefloquine, but had no significant effect on sensitivity to chloroquine, amodiaquine, piperaquine, and artesunate. To our knowledge, this is the first reported use of CRISPR-Cas9 in P. cynomolgi, and the first reported integrative genetic manipulation of this species. Oxford University Press 2022-12-07 /pmc/articles/PMC10175063/ /pubmed/36478252 http://dx.doi.org/10.1093/infdis/jiac469 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article Ward, Kurt E Christensen, Peter Racklyeft, Annie Dhingra, Satish K Chua, Adeline C Y Remmert, Caroline Suwanarusk, Rossarin Matheson, Jessica Blackman, Michael J Kaneko, Osamu Kyle, Dennis E Lee, Marcus C S Moon, Robert W Snounou, Georges Rénia, Laurent Fidock, David A Russell, Bruce Bifani, Pablo Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title | Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title_full | Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title_fullStr | Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title_full_unstemmed | Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title_short | Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine |
title_sort | integrative genetic manipulation of plasmodium cynomolgi reveals multidrug resistance-1 y976f associated with increased in vitro susceptibility to mefloquine |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175063/ https://www.ncbi.nlm.nih.gov/pubmed/36478252 http://dx.doi.org/10.1093/infdis/jiac469 |
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